Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

RECORD: Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00379769
First received: September 21, 2006
Last updated: November 6, 2014
Last verified: December 2013
Results First Received: August 24, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Rosiglitazone
Drug: Sulfonylurea
Drug: Metformin

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The RECORD study ran from April 2001 through December 2008. Results are presented in the non-re-adjudicated outcome measures (OMs). An independent patient-level re-adjudication of mortality, non-fatal myocardial infarction, and non-fatal stroke began on January 2011 and ran through March 2012. The results are presented in the re-adjudicated OMs.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The RECORD observational follow-up (OFU) started at the end of the RECORD study and ran through December 2012. OFU was designed to collect cancer and bone fracture data. Participants were not provided with study medication in the OFU. Data are presented for the entire study (RECORD + OBF) and for OFU alone in the observational OMs.

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Participant Flow for 2 periods

Period 1:   Main Study
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
STARTED     1117     1105     1103     1122     0     0  
COMPLETED     939     906     896     892     0     0  
NOT COMPLETED     178     199     207     230     0     0  
Death                 57                 67                 54                 72                 0                 0  
Adverse Event                 5                 8                 10                 11                 0                 0  
Lost to Follow-up                 29                 29                 25                 26                 0                 0  
Withdrawal by Subject                 46                 56                 72                 70                 0                 0  
Moved to survival status follow-up only                 27                 25                 32                 36                 0                 0  
Participant moved                 3                 2                 3                 3                 0                 0  
Poor compliance                 3                 2                 2                 1                 0                 0  
Prohibited glucose lowering medication                 0                 3                 0                 1                 0                 0  
Site closed                 4                 4                 4                 8                 0                 0  
Entry criteria violation                 0                 0                 1                 1                 0                 0  
Participant did not take study drug                 0                 0                 1                 0                 0                 0  
Physician Decision                 2                 2                 1                 1                 0                 0  
Participant completed study at visit 27                 1                 0                 0                 0                 0                 0  
Personal reasons                 1                 0                 0                 0                 0                 0  
Risk of heart failure                 0                 1                 0                 0                 0                 0  
Investigator refused to log temperature                 0                 0                 1                 0                 0                 0  
Reason unspecified                 0                 0                 1                 0                 0                 0  

Period 2:   Observational Follow-up
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
STARTED     0     0     0     0     1280 [1]   1250 [2]
COMPLETED     0     0     0     0     1131     1102  
NOT COMPLETED     0     0     0     0     149     148  
Death                 0                 0                 0                 0                 78                 70  
Adverse Event                 0                 0                 0                 0                 1                 0  
Lost to Follow-up                 0                 0                 0                 0                 25                 27  
Withdrawal by Subject                 0                 0                 0                 0                 12                 12  
Entered into Another Clinical Trial                 0                 0                 0                 0                 18                 22  
Physician Decision                 0                 0                 0                 0                 8                 8  
Site Closed Early                 0                 0                 0                 0                 6                 7  
Participant Moved                 0                 0                 0                 0                 0                 1  
Unknown; Reason Not Provided                 0                 0                 0                 0                 1                 1  
[1] 665 from “RSG in Addition to Background MET” arm; 615 from “RGS in Addition to Background SU” arm.
[2] 647 from “SU in Addition to Background MET” arm; 603 from “MET in Addition to Background SU” arm.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Total Total of all reporting groups

Baseline Measures
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Total  
Number of Participants  
[units: participants]
  1117     1105     1103     1122     4447  
Age  
[units: years]
Mean ± Standard Deviation
  57.0  ± 8.02     57.2  ± 8.14     59.8  ± 8.26     59.7  ± 8.23     58.4  ± 8.27  
Gender  
[units: participants]
         
Female     516     521     562     554     2153  
Male     601     584     541     568     2294  
Race/Ethnicity, Customized  
[units: participants]
         
White     1105     1087     1095     1112     4399  
Black     3     6     2     3     14  
Oriental     4     2     5     7     18  
Aboriginal     1     0     0     0     1  
African     1     0     0     0     1  
Asian     1     2     1     0     4  
Egyptian     1     0     0     0     1  
Gipsy     1     0     0     0     1  
Indian     0     1     0     0     1  
Maori     0     1     0     0     1  
Middle East Hible     0     1     0     0     1  
Pacific Islander     0     1     0     0     1  
Polynesian     0     1     0     0     1  
Sri Lankan     0     2     0     0     2  
Tahitian     0     1     0     0     1  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events
Measure Description The number of participants with cardiovascular death events (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation events (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) was recorded.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events  
[units: participants]
  321     323  


Statistical Analysis 1 for Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Hazard Ratio (HR) [3] 0.99
95% Confidence Interval ( 0.85 to 1.16 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority margin of 1.2 for the upper limit of the 95 percent confidence interval in time to event analysis comparing RSG to MET/SU stratified by background medication
[3] Other relevant estimation information:
  No text entered.



2.  Primary:   Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause
Measure Description All deaths identified during the original record study and discovered after the re-adjudication efforts began were included.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause  
[units: participants]
  139     160  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause
Groups [1] All groups
Hazard Ratio (HR) [2] 0.86
95% Confidence Interval ( 0.68 to 1.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



3.  Primary:   Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions
Measure Description IR was based on original RECORD endpoint definitions. CV death= no unequivocal non-CV cause (sudden death, death from acute vascular events, heart failure, acute MI, other CV causes, and deaths adjudicated as unknown cause). MI event=hospitalization + elevation of specific cardiac biomarkers above the upper limit of normal + cardiac ischemia symptoms/new pathological electrocardiogram findings. Stroke event=hospitalization + rapidly developed clinical signs of focal/global disturbance of cerebral function for more than 24 hours, with no apparent cause other than a vascular origin.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions  
[units: participants]
  181     188  


Statistical Analysis 1 for Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 0.95
95% Confidence Interval ( 0.78 to 1.17 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



4.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions
Measure Description Independent re-adjudication was based on the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions. CV death included death resulting from an acute MI; sudden cardiac death and death due to heart failure, stroke, and to other CV causes. Deaths of unknown cause were counted as CV deaths. MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions  
[units: participants]
  186     191  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 0.97
95% Confidence Interval ( 0.79 to 1.18 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



5.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions
Measure Description The number of participants with a CV death (or unknown) as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. CV death was defined as any death for which an unequivocal non-CV cause could not be established. CV death included death following heart failure, death following acute myocardial infarction (MI), sudden death, death due to acute vascular events, and other CV causes. Deaths due to unknown causes were classified as "unknown deaths," but were counted as CV deaths for the analysis of this endpoint.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions  
[units: participants]
  88     96  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 0.90
95% Confidence Interval ( 0.68 to 1.21 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



6.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions
Measure Description The number of participants with a CV (or unknown) death as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. CV death included death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, and death due to other CV causes. Deaths of unknown cause were counted as CV deaths.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions  
[units: participants]
  88     96  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 0.90
95% Confidence Interval ( 0.68 to 1.21 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



7.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
Measure Description The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. An event of MI was defined as hospitalization plus elevation of cardiac biomarkers troponin (TN) I and/or TNT above the upper limit of normal (ULN) or creatinine kinase (CK) MB (M=muscle type; B=brain type) isoenzyme >= 2x the ULN or CK > 2x the ULN plus typical symptoms of cardiac ischemia or new pathological electrocardiogram findings, or cause of death adjudicated as MI.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions  
[units: participants]
  68     60  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 1.13
95% Confidence Interval ( 0.80 to 1.59 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



8.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
Measure Description The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions  
[units: participants]
  72     62  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 1.15
95% Confidence Interval ( 0.82 to 1.62 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



9.  Primary:   Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
Measure Description Par. with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. A stroke event=hospitalization plus rapidly developed clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by thrombolysis, surgery, or death), with no apparent cause other than a vascular origin, including par. presenting clinical signs/symptoms suggestive of subarachnoid haemorrhage/intracerebral haemorrhage/cerebral ischemic necrosis or cause of death adjudicated as stroke.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions  
[units: participants]
  50     63  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 0.79
95% Confidence Interval ( 0.54 to 1.14 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



10.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Primary
Measure Title Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
Measure Description The number of participants with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions  
[units: participants]
  53     64  


Statistical Analysis 1 for Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
Groups [1] All groups
Hazard Ratio (HR) [2] 0.82
95% Confidence Interval ( 0.57 to 1.18 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



11.  Secondary:   Number of Participants With Cardiovascular Events and All-cause Deaths   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Secondary
Measure Title Number of Participants With Cardiovascular Events and All-cause Deaths
Measure Description Composites of participants with first cardiovascular (CV) hospitalisations and CV death or all-cause death and individual first events of acute myocardial infarction (MI) , stroke, congestive heart failure (CHF), CV death, and all-cause death.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With Cardiovascular Events and All-cause Deaths  
[units: participants]
   
CV death, acute MI, stroke     154     165  
CV death, acute MI, stroke, unstable angina     171     184  
CV death, acute MI, stroke, unstable angina, CHF     204     206  
All-cause death,acuteMI,stroke,unstable angina,CHF     251     268  
Acute MI (fatal or non-fatal)     64     56  
Stroke (fatal or non-fatal)     46     63  
CHF (fatal or non-fatal)     61     29  
Death from CV causes     60     71  
Death (all cause) during CV follow-up     111     139  
Death (all-cause) including survival status     136     157  

No statistical analysis provided for Number of Participants With Cardiovascular Events and All-cause Deaths



12.  Secondary:   Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Secondary
Measure Title Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths
Measure Description The total number of events for individual components of cardiovascular (CV) hospitalisations and cardiovascular deaths were recorded. MI, myocardial infarction.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths  
[units: Number of events]
   
CV deaths     60     71  
Death due to acute MI     7     10  
Death due to heart failure     10     2  
Sudden death     8     12  
Death due to acute vascular events     1     10  
Other CV mortality     6     4  
Death of presumed CV cause     28     33  
Cardiovascular hospitalisation     483     490  
Hospitalisation for acute MI     66     57  
Hospitalisation for unstable angina     28     28  
Hospitalisation for congestive heart failure     69     36  
Hospitalisation for stroke     51     67  
Hospitalisation for transient ischaemic attack     10     10  
Hospitalisation for invasive CV procedure     99     116  
Hospitalisation for amputation of extremities     6     23  
Other CV hospitalisations     154     153  

No statistical analysis provided for Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths



13.  Secondary:   Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Secondary
Measure Title Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum
Measure Description Participants with first cardiovascular death (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) were recorded by study stratum.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1117     1105     1103     1122  
Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum  
[units: partcipants]
  158     154     163     169  

No statistical analysis provided for Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum



14.  Secondary:   Number of Participants With CV/Microvascular Events   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Secondary
Measure Title Number of Participants With CV/Microvascular Events
Measure Description The number of participants with first cardiovascular or microvascular events (renal, foot, eye) were recorded.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
Combined RSG Participants inadequately controlled on background MET or background SU were randomised to receive RSG, in addition to MET or SU. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined MET/SU Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent. Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    Combined RSG     Combined MET/SU  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With CV/Microvascular Events  
[units: participants]
   
Participants with a CV/Microvascular event     363     385  
Participants with any microvascular event     59     78  
Participants with any eye event     42     52  
Participants with any foot event     19     28  
Participants with any renal event     0     0  

No statistical analysis provided for Number of Participants With CV/Microvascular Events



15.  Secondary:   Number of Participants With Glycaemic Failure Events   [ Time Frame: Baseline through to end of randomised dual therapy ]

Measure Type Secondary
Measure Title Number of Participants With Glycaemic Failure Events
Measure Description Failure of glycaemic control was defined as two consecutive HbA1c values of ≥8.5 percent, or HbA1c ≥8.5percent at a single visit, after which the subject was either moved to the post-randomised treatment phase or triple therapy was started.
Time Frame Baseline through to end of randomised dual therapy  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1117     1105     1103     1122  
Number of Participants With Glycaemic Failure Events  
[units: participants]
  281     451     365     424  

No statistical analysis provided for Number of Participants With Glycaemic Failure Events



16.  Secondary:   Number of Participants With Addition of Third Oral Agent/Switch to Insulin   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Secondary
Measure Title Number of Participants With Addition of Third Oral Agent/Switch to Insulin
Measure Description The number of participants with addition of a third oral agent or switch to insulin from randomised dual combination treatment were recorded.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1117     1105     1103     1122  
Number of Participants With Addition of Third Oral Agent/Switch to Insulin  
[units: participants]
       
Participants with an event     295     183     344     171  
First Event - Triple Therapy     257     7     296     6  
First Event - Insulin     38     176     49     165  

No statistical analysis provided for Number of Participants With Addition of Third Oral Agent/Switch to Insulin



17.  Secondary:   The Number of Participants Starting Insulin at Any Time During the Study   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Measure Type Secondary
Measure Title The Number of Participants Starting Insulin at Any Time During the Study
Measure Description The number of participants starting insulin at any time during the study was recorded.
Time Frame Baseline through End of Study (up to 7.5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1117     1105     1103     1122  
The Number of Participants Starting Insulin at Any Time During the Study  
[units: participants]
  126     276     168     259  

No statistical analysis provided for The Number of Participants Starting Insulin at Any Time During the Study



18.  Secondary:   Model Adjusted Change From Baseline in HbA1c at Month 60   [ Time Frame: Baseline and Month 60 of randomised dual therapy treatment period ]

Measure Type Secondary
Measure Title Model Adjusted Change From Baseline in HbA1c at Month 60
Measure Description Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in HbA1c was calculated as the value at Month 60 minus the Baseline value.
Time Frame Baseline and Month 60 of randomised dual therapy treatment period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1096     1079     1073     1079  
Model Adjusted Change From Baseline in HbA1c at Month 60  
[units: Percent]
Mean ± Standard Error
  -0.14  ± 0.035     0.17  ± 0.042     -0.24  ± 0.039     -0.10  ± 0.039  

No statistical analysis provided for Model Adjusted Change From Baseline in HbA1c at Month 60



19.  Secondary:   Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

Measure Type Secondary
Measure Title Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60
Measure Description Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in fasting plasma glucose was calculated as the value at Month 60 minus the Baseline value.
Time Frame Baseline to Month 60 of the randomised dual therapy treatment period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1095     1078     1074     1079  
Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60  
[units: mmol/L (millimoles/Liter)]
Mean ± Standard Error
  -1.38  ± 0.073     -0.29  ± 0.090     -2.00  ± 0.085     -0.94  ± 0.094  

No statistical analysis provided for Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60



20.  Secondary:   Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

Measure Type Secondary
Measure Title Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60
Measure Description Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in insulin and pro-insulin was calculated as the value at Month 60 minus the Baseline value.
Time Frame Baseline to Month 60 of the randomised dual therapy treatment period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  931     982     882     940  
Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60  
[units: picamoles/liter (pmol/L)]
Mean ± Standard Error
       
Insulin, Adjusted Change from Baseline     -18.6  ± 1.01     3.7  ± 1.77     -16.9  ± 1.65     -12.1  ± 1.91  
Pro-insulin, Adjusted Change from Baseline     -2.4  ± 0.26     4.2  ± 0.43     -3.2  ± 0.48     -3.0  ± 0.37  

No statistical analysis provided for Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60



21.  Secondary:   Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

Measure Type Secondary
Measure Title Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60
Measure Description Number of responders, i.e., participants meeting glycaemic targets (HbA1c less than or equal to 7 percent, FPG less than or equal to 7 mmol/L)
Time Frame Baseline to Month 60 of the randomised dual therapy treatment period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1117     1105     1103     1122  
Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60  
[units: participants]
       
HbA1c Responders     265     208     235     180  
FPG Responders     300     180     257     154  

No statistical analysis provided for Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60



22.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in HOMA beta-cell function and insulin sensitivity was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  926     977     878     933  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
       
Beta cell function     20.54  
  ( 16.52 to 24.70 )  
  19.28  
  ( 14.66 to 24.09 )  
  32.35  
  ( 26.55 to 38.41 )  
  12.43  
  ( 7.42 to 17.67 )  
Insulin sensitivity     42.57  
  ( 37.57 to 47.76 )  
  -3.45  
  ( -7.21 to 0.47 )  
  42.07  
  ( 36.39 to 47.98 )  
  23.90  
  ( 19.36 to 28.61 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60



23.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC, LDL cholesterol, HDL cholesterol, triglycerides, and FFAs was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1117     1105     1103     1122  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
       
Total cholesterol     -5.49  
  ( -6.99 to -3.96 )  
  -9.09  
  ( -10.33 to -7.84 )  
  -2.91  
  ( -4.62 to -1.17 )  
  -9.68  
  ( -11.03 to -8.31 )  
HDL-cholesterol     9.95  
  ( 8.44 to 11.49 )  
  2.57  
  ( 1.46 to 3.68 )  
  7.73  
  ( 6.18 to 9.30 )  
  6.14  
  ( 4.88 to 7.42 )  
LDL-cholesterol     -12.70  
  ( -15.03 to -10.30 )  
  -17.68  
  ( -19.70 to -15.61 )  
  -8.99  
  ( -11.42 to -6.49 )  
  -17.80  
  ( -19.93 to -15.61 )  
Triglycerides     -7.97  
  ( -10.72 to -5.15 )  
  -1.95  
  ( -4.73 to 0.91 )  
  -2.68  
  ( -5.69 to 0.43 )  
  -2.50  
  ( -5.21 to 0.28 )  
Free fatty acids     -16.46  
  ( -19.13 to -13.71 )  
  2.79  
  ( -0.23 to 5.91 )  
  -11.58  
  ( -14.65 to -8.41 )  
  4.47  
  ( 1.23 to 7.81 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60



24.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC:HDL cholesterol and LDL cholesterol:HDL cholesterol was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1117     1105     1103     1122  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
       
Total Cholesterol: HDL Cholesterol Ratio     -14.20  
  ( -15.98 to -12.39 )  
  -11.33  
  ( -12.82 to -9.81 )  
  -9.93  
  ( -11.83 to -7.98 )  
  -15.01  
  ( -16.44 to -13.55 )  
LDL Cholesterol: HDL-Cholesterol Ratio     -20.89  
  ( -23.24 to -18.46 )  
  -20.04  
  ( -22.16 to -17.87 )  
  -15.85  
  ( -18.26 to -13.37 )  
  -22.53  
  ( -24.63 to -20.37 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60



25.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in Apo-B was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  949     1007     906     970  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
  -13.77  
  ( -15.45 to -12.05 )  
  -11.63  
  ( -13.10 to -10.14 )  
  -9.68  
  ( -11.55 to -7.77 )  
  -12.09  
  ( -13.67 to -10.47 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60



26.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in urinary albumin creatinine ratio was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  899     921     891     901  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
  8.31  
  ( -0.70 to 18.14 )  
  15.17  
  ( 6.73 to 24.28 )  
  -3.43  
  ( -11.91 to 5.87 )  
  11.91  
  ( 3.10 to 21.46 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60



27.  Secondary:   Model Adjusted Change From Baseline in Body Weight at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Change From Baseline in Body Weight at Month 60
Measure Description Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in body weight was calculated as the value at Month 60 minus the Baseline value.
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive RSG, in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or miconizied equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1096     1079     1073     1079  
Model Adjusted Change From Baseline in Body Weight at Month 60  
[units: kilograms]
Mean ± Standard Error
  3.93  ± 0.263     -0.54  ± 0.192     4.72  ± 0.235     -2.16  ± 0.179  

No statistical analysis provided for Model Adjusted Change From Baseline in Body Weight at Month 60



28.  Secondary:   Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60
Measure Description Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in alanine aminotransferase was calculated as the value at Month 60 minus the Baseline value.
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive RSG, in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or miconizied equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1094     1077     1073     1078  
Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60  
[units: U/L (Units/Liter)]
Mean ( 95% Confidence Interval )
  -37.43  
  ( -39.22 to -35.59 )  
  -21.73  
  ( -23.90 to -19.50 )  
  -30.17  
  ( -31.98 to -28.31 )  
  -24.00  
  ( -26.21 to -21.73 )  

No statistical analysis provided for Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60



29.  Secondary:   Model Adjusted Change From Baseline in Waist Circumference at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Change From Baseline in Waist Circumference at Month 60
Measure Description Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in waist circumference was calculated as the value at Month 60 minus the Baseline value.
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive RSG, in addition to MET. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15mg per day or miconizied equivalent of 10.5mg per day; gliclazide 240mg per day and glimepiride 4mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  972     1032     926     994  
Model Adjusted Change From Baseline in Waist Circumference at Month 60  
[units: cm (centimeters)]
Mean ± Standard Error
  2.70  ± 0.266     0.65  ± 0.214     3.00  ± 0.263     -0.60  ± 0.215  

No statistical analysis provided for Model Adjusted Change From Baseline in Waist Circumference at Month 60



30.  Secondary:   Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60
Measure Description Model adjusted (adjusted for any imbalances in the baseline values between within treatment groups) change from baseline in SBP and DBP was calculated as the value at Month 60 minus the Baseline value.
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive RSG, in addition to MET. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15mg per day or miconizied equivalent of 10.5mg per day; gliclazide 240mg per day and glimepiride 4mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  1096     1079     1074     1079  
Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60  
[units: mmHg (millimeters of mercury)]
Mean ± Standard Error
       
SBP     -1.9  ± 0.54     -2.2  ± 0.52     -2.3  ± 0.52     -0.6  ± 0.53  
DBP     -3.6  ± 0.34     -3.4  ± 0.29     -3.6  ± 0.31     -2.3  ± 0.31  

No statistical analysis provided for Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60



31.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in C-Reactive Protein was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive RSG, in addition to MET. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15mg per day or miconizied equivalent of 10.5mg per day; gliclazide 240mg per day and glimepiride 4mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  942     987     887     952  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
  -57.40  
  ( -60.41 to -54.15 )  
  -28.92  
  ( -33.71 to -23.79 )  
  -56.50  
  ( -61.56 to -55.21 )  
  -36.29  
  ( -41.03 to -31.17 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60



32.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in fibrinogen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive RSG, in addition to MET. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15mg per day or miconizied equivalent of 10.5mg per day; gliclazide 240mg per day and glimepiride 4mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  918     987     875     941  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
  2.12  
  ( 0.54 to 3.72 )  
  5.74  
  ( 4.22 to 7.28 )  
  -0.23  
  ( -1.79 to 1.35 )  
  3.14  
  ( 1.38 to 4.93 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60



33.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Measure Type Secondary
Measure Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60
Measure Description The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in plasminogen activator inhibitor-1 (PAI-1) antigen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]).
Time Frame Baseline to Month 60 of the randomised dual therapy treatment phase  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive RSG, in addition to MET. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, an SU (glibenclamide, gliclazide or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15mg per day or miconizied equivalent of 10.5mg per day; gliclazide 240mg per day and glimepiride 4mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4mg once daily dose and was increased to a maximum dose of 8mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU  
Number of Participants Analyzed  
[units: participants]
  931     991     882     939  
Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60  
[units: percent change]
Geometric Mean ( 95% Confidence Interval )
  -9.85  
  ( -14.42 to -5.02 )  
  15.01  
  ( 9.77 to 20.50 )  
  -7.79  
  ( -12.61 to -2.71 )  
  -0.64  
  ( -5.82 to 4.83 )  

No statistical analysis provided for Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60



34.  Secondary:   Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined  
[units: participants]
   
All neoplasms/cancer (N/C) (benign/malignant)     196     215  
Malignant (Mal.) N/C     179     195  
Mal. N/C; excluding non-melanomatous skin cancers     164     186  

No statistical analysis provided for Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined



35.  Secondary:   Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up  
[units: participants]
   
All neoplasms/cancer (N/C) (benign/malignant)     60     51  
Malignant (Mal.) N/C     59     51  
Mal. N/C; excluding non-melanomatous skin cancers     55     46  

No statistical analysis provided for Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up



36.  Secondary:   Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined
Measure Description The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined  
[units: participants]
   
Any genitourinary     57     57  
Prostate     22     22  
Renal     12     9  
Uterine     11     16  
Bladder     8     5  
Vaginal/vulvar     1     1  
Ovarian     5     4  
Any gastrointestinal     48     62  
Colon/rectal cancer     22     30  
Colon     14     21  
Gastric     13     5  
Pancreatic     5     16  
Liver     4     5  
Gall bladder/biliary     4     5  
Gastrointestinal; not specified     0     1  
Any hematologic     12     6  
Lung     19     15  
Skin (non-melanomatous)     19     13  
Skin (melanomatous)     6     4  
Metastases     12     18  
Breast     12     23  
Head and neck     4     7  
Neurologic     3     3  
Endocrine     3     6  
Not specified     0     1  
Other     0     3  

No statistical analysis provided for Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined



37.  Secondary:   Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up
Measure Description The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up  
[units: participants]
   
Any genitourinary     18     8  
Prostate     7     1  
Renal     5     2  
Uterine     4     4  
Bladder     2     0  
Vaginal/vulvar     0     1  
Ovarian     0     0  
Any gastrointestinal     17     19  
Colon/rectal cancer     5     11  
Colon     2     7  
Gastric     5     1  
Pancreatic     4     3  
Liver     2     2  
Gall bladder/biliary     1     1  
Gastrointestinal; not specified     0     1  
Any hematologic     6     1  
Lung     6     6  
Skin (non-melanomatous)     6     5  
Skin (melanomatous)     3     2  
Metastases     3     6  
Breast     2     7  
Head and neck     2     1  
Neurologic     1     1  
Endocrine     0     1  
Not specified     0     0  
Other     0     0  

No statistical analysis provided for Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up



38.  Secondary:   Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined  
[units: participants]
   
Any cancer-related death     59     72  
Any gastrointestinal event     25     34  
Pancreatic     4     12  
Colon/rectal     6     11  
Gastric     7     3  
Liver     4     4  
Gall bladder/biliary     4     3  
Gastrointestinal event; not specified     0     1  
Any genitourinary event     6     15  
Renal     2     3  
Uterine     1     5  
Prostate     1     2  
Bladder     1     3  
Ovarian     1     2  
Lung     13     11  
Any hematologic event     4     0  
Skin (melanoma)     3     0  
Skin (non-melanomatous)     1     0  
Metastases     2     4  
Breast     2     3  
Head and neck     1     2  
Any neurologic event     2     2  
Endocrine     1     0  
Not specified     0     1  

No statistical analysis provided for Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined



39.  Secondary:   Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up  
[units: participants]
   
Any cancer-related death     25     24  
Any gastrointestinal event     10     14  
Pancreatic     3     3  
Colon/rectal     2     6  
Gastric     2     1  
Liver     2     2  
Gall bladder/biliary     1     1  
Gastrointestinal event; not specified     0     1  
Any genitourinary event     2     0  
Renal     1     0  
Uterine     1     0  
Prostate     0     0  
Bladder     0     0  
Ovarian     0     0  
Lung     4     5  
Any hematologic event     4     0  
Skin (melanoma)     1     0  
Skin (non-melanomatous)     1     0  
Metastases     1     1  
Breast     1     3  
Head and neck     1     0  
Any neurologic event     1     1  
Endocrine     0     0  
Not specified     0     0  

No statistical analysis provided for Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up



40.  Secondary:   Number of Participants With a Bone Fracture Event – Overall and by Gender: Main Study and Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With a Bone Fracture Event – Overall and by Gender: Main Study and Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With a Bone Fracture Event – Overall and by Gender: Main Study and Observational Follow-up Combined  
[units: participants]
   
Overall, n=2220, 2227     238     151  
Male, n=1142, 1152     82     60  
Female, n=1078, 1075     156     91  

No statistical analysis provided for Number of Participants With a Bone Fracture Event – Overall and by Gender: Main Study and Observational Follow-up Combined



41.  Secondary:   Number of Participants With a Bone Fracture Event – Overall and by Gender: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants With a Bone Fracture Event – Overall and by Gender: Observational Follow-up
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants With a Bone Fracture Event – Overall and by Gender: Observational Follow-up  
[units: participants]
   
Overall, n=1280, 1250     64     37  
Male, n=665, 635     25     11  
Female, n=615, 615     39     26  

No statistical analysis provided for Number of Participants With a Bone Fracture Event – Overall and by Gender: Observational Follow-up



42.  Secondary:   Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined
Measure Description The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined  
[units: participants]
   
Any event     81     57  
Upper limb     41     17  
Distal lower limb     24     16  
Femur/hip     15     11  
Spinal     7     9  
Pelvic     0     3  
Other     7     4  

No statistical analysis provided for Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined



43.  Secondary:   Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up
Measure Description The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up  
[units: participants]
   
Any event     35     21  
Upper limb     17     5  
Distal lower limb     9     8  
Femur/hip     6     4  
Spinal     2     3  
Pelvic     0     1  
Other     2     1  

No statistical analysis provided for Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up



44.  Secondary:   Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined  
[units: participants]
  0     0  

No statistical analysis provided for Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined



45.  Secondary:   Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined  
[units: participants]
   
Any event, overall; n=2220, 2227     238     151  
Any event, male; n=1142, 1152     82     60  
Any event, female; n=1078, 1075     156     91  
Upper limb, any event, overall; n=2220, 2227     116     70  
Upper limb, any event, male; n=1142, 1152     32     22  
Upper limb, any event, female; n=1078, 1075     84     48  
Distal lower limb, any event, overall; n=2220, 222     88     40  
Distal lower limb, any event, male; n=1142, 1152     31     14  
Distal lower limb, any event, female; n=1078, 1075     57     26  
Femur/hip, any event, overall; n=2220, 2227     16     13  
Femur/hip, any event, male; n=1142, 1152     4     1  
Femur/hip, any event, female; n=1078, 1075     12     12  
Spinal, any event, overall; n=2220, 2227     18     14  
Spinal, any event, male; n=1142, 1152     7     9  
Spinal, any event, female; n=1078, 1075     11     5  
Pelvic, any event, overall; n=2220, 2227     0     5  
Pelvic, any event, male; n=1142, 1152     0     4  
Pelvic, any event, female; n=1078, 1075     0     1  
Unclassified, any event, overall; n=2220, 2227     1     0  
Unclassified, any event, male; n=1142, 1152     1     0  
Unclassified, any event, female; n=1078, 1075     0     0  
Other, any event, overall; n=2220, 2227     31     26  
Other, any event, male; n=1142, 1152     18     16  
Other, any event, female; n=1078, 1075     13     10  

No statistical analysis provided for Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined



46.  Secondary:   Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up  
[units: participants]
   
Any event, overall; n=1280, 1250     64     37  
Any event, male; n=665, 635     25     11  
Any event, female; n=615, 615     39     26  
Upper limb, any event, overall; n=1280, 1250     33     15  
Upper limb, any event, male; n=665, 635     10     3  
Upper limb, any event, female; n=615, 615     23     12  
Distal lower limb, any event, overall; n=1280,1250     18     13  
Distal lower limb, any event, male; n=665, 635     9     4  
Distal lower limb, any event, female; n=615, 615     9     9  
Femur/hip, any event, overall; n=1280, 1250     6     5  
Femur/hip, any event, male; n=665, 635     1     0  
Femur/hip, any event, female; n=615, 615     5     5  
Spinal, any event, overall; n=1280, 1250     4     5  
Spinal, any event, male; n=665, 635     1     4  
Spinal, any event, female; n=615, 615     3     1  
Pelvic, any event, overall; n=1280, 1250     0     1  
Pelvic, any event, male; n=665, 635     0     1  
Pelvic, any event, female; n=615, 615     0     0  
Unclassified, any event, overall; n=1280, 1250     1     0  
Unclassified, any event, male; n=665, 635     1     0  
Unclassified, any event, female; n=615, 615     0     0  
Other, any event, overall; n=1280, 1250     6     1  
Other, any event, male; n=665, 635     4     1  
Other, any event, female; n=615, 615     2     0  

No statistical analysis provided for Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up



47.  Secondary:   Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown).
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined  
[units: participants]
   
Any event, overall, n=2220, 2227     31     31  
Any event, male, n=1142, 1152     10     13  
Any event, female, n=1078, 1075     21     18  
Hip, overall, n=2220, 2227     9     7  
Hip, male, n=1142, 1152     0     1  
Hip, female, n=1078, 1075     9     6  
Pelvis, overall, n=2220, 2227     0     5  
Pelvis, male, n=1142, 1152     0     4  
Pelvis, female, n=1078, 1075     0     1  
Upper leg, overall, n=2220, 2227     7     6  
Upper leg, male, n=1142, 1152     4     0  
Upper leg, female, n=1078, 1075     3     6  
Any vertebral event, overall, n=2220, 2227     16     13  
Any vertebral event, male, n=1142, 1152     6     8  
Any vertebral event, female, n=1078, 1075     10     5  
Lumbar spine, overall, n=2220, 2227     10     4  
Lumbar spine, male, n=1142, 1152     5     3  
Lumbar spine, female, n=1078, 1075     5     1  
Thoracic spine, overall, n=2220, 2227     5     8  
Thoracic spine, male, n=1142, 1152     1     4  
Thoracic spine, female, n=1078, 1075     4     4  
Cervical spine, overall, n=2220, 2227     1     1  
Cervical spine, male, n=1142, 1152     0     1  
Cervical spine, female, n=1078, 1075     1     0  

No statistical analysis provided for Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined



48.  Secondary:   Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown).
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined  
[units: participants]
   
Any H/UA/FF event, overall, n=2220, 2227     86     46  
Any H/UA/FF event, male, n=1142, 1152     28     15  
Any H/UA/FF event, female, n=1078, 1075     58     31  
High morbidity fractures, overall, n=2220, 2227     5     1  
High morbidity fractures, male, n=1142, 1152     0     0  
High morbidity fractures, female, n=1078, 1075     5     1  
Non-high morbidity fractures, overall, n=2220, 222     15     4  
Non-high morbidity fractures, male, n=1142, 1152     2     3  
Non-high morbidity fractures, female, n=1078, 1075     13     1  

No statistical analysis provided for Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined



49.  Secondary:   Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant.
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined  
[units: participants]
   
Any event     238     151  
Non-traumatic event     113     55  
Traumatic event     110     77  
Pathologic     1     4  
Unknown     20     19  
Data unavailable     9     3  

No statistical analysis provided for Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined



50.  Secondary:   Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included "Unknown" as a category. Fracture events with missing outcome data were reported as "Data unavailable."
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up  
[units: participants]
   
Any event     64     37  
Non-traumatic event,     36     14  
Traumatic event     24     17  
Pathologic     1     2  
Unknown     1     4  
Data unavailable     3     1  

No statistical analysis provided for Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up



51.  Secondary:   Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

Measure Type Secondary
Measure Title Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included "Unknown" as a category. Fracture events with missing outcome data were reported as "Data unavailable."
Time Frame From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Main Study and Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Main Study and Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Main Study and Observational Follow-up     Combined MET/SU: Main Study and Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  2220     2227  
Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined  
[units: bone fracture events]
   
Number of bone fracture events     299     174  
Unknown     7     5  
Normal healing with standard management     250     142  
Complication     14     13  
Additional therapeutic measures required     16     9  
Data unavailable     12     5  

No statistical analysis provided for Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined



52.  Secondary:   Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included "Unknown" as a category. Fracture events with missing outcome data were reported as "Data unavailable."
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up  
[units: bone fracture events]
   
Number of bone fracture events     70     41  
Unknown     1     1  
Normal healing with standard management     51     33  
Complication     7     4  
Additional therapeutic measures required     3     2  
Data unavailable     8     1  

No statistical analysis provided for Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up



53.  Secondary:   Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up
Measure Description The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE.
Time Frame From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observational Follow-up Population: all participants from the ITT Population of the RECORD study who provided data during the observational follow-up. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).

Reporting Groups
  Description
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Measured Values
    Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Number of Participants Analyzed  
[units: participants]
  1280     1250  
Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up  
[units: participants]
   
Any event     99     76  
Ankle fracture     6     3  
Prostate cancer     7     1  
Lung neoplasm malignant     4     4  
Breast cancer     2     6  
Basal cell carcinoma     4     3  
Pancreatic carcinoma     4     3  
Colon cancer     1     6  
Humerus fracture     5     1  
Upper limb fracture     5     1  
Malignant melanoma     3     2  
Uterine cancer     2     3  
Gastric cancer     4     0  
Wrist fracture     4     0  
Hip fracture     3     1  
Radius fracture     3     1  
Forearm fracture     2     2  
Hepatic neoplasm malignant     2     2  
Rectal cancer     2     2  
Renal cancer     2     2  
Foot fracture     1     3  
Renal cell carcinoma     3     0  
Femur fracture     2     1  
Femoral neck fracture     1     2  
Lumbar vertebral fracture     1     2  
Metastases to bone     1     2  
Metastases to liver     1     2  
Bladder cancer     2     0  
Fall     2     0  
Metastases to central nervous system     2     0  
Rib fracture     2     0  
Squamous cell carcinoma     2     0  
Acute myocardial infarction     1     1  
Brain neoplasm     1     1  
Gastric neoplasm     1     1  
Metastases to lung     1     1  
Patella fracture     1     1  
Death     0     2  
Abdominal pain     1     0  
Acute myeloid leukaemia     1     0  
Acute respiratory failure     1     0  
Anaemia     1     0  
Benign salivary gland neoplasm     1     0  
Biliary colic     1     0  
Biliary neoplasm     1     0  
Bone neoplasm malignant     1     0  
Bronchial carcinoma     1     0  
Cardiac failure acute     1     0  
Chest pain     1     0  
Chronic lymphocytic leukaemia     1     0  
Colon neoplasm     1     0  
Contusion     1     0  
Drowning     1     0  
Dysplasia     1     0  
Endometrial cancer stage I     1     0  
Leukaemia     1     0  
Lower limb fracture     1     0  
Lung squamous cell carcinoma stage unspecified     1     0  
Lymphoma     1     0  
Malignant neoplasm of pleura     1     0  
Metastases to skin     1     0  
Metastases to testicle     1     0  
Metastatic renal cell carcinoma     1     0  
Oesophageal carcinoma     1     0  
Osteoarthritis     1     0  
Pancreatic necrosis     1     0  
Rectal cancer stage II     1     0  
Spinal fracture     1     1  
T-cell lymphoma     1     1  
Urinary tract infection     1     1  
Uterine leiomyosarcoma     1     0  
Biliary cancer metastatic     0     1  
Cervix carcinoma     0     1  
Chronic obstructive pulmonary disease     0     1  
Comminuted fracture     0     1  
Craniocerebral injury     0     1  
Gastrointestinal neoplasm     0     1  
Hepatic lesion     0     1  
Joint dislocation     0     1  
Laryngeal cancer     0     1  
Lip neoplasm malignant stage unspecified     0     1  
Lung neoplasm     0     1  
Metastases to lymph nodes     0     1  
Metastasis     0     1  
Musculoskeletal chest pain     0     1  
Myocardial infarction     0     1  
Non-Hodgkin's lymphoma     0     1  
Pubis fracture     0     1  
Pulmonary embolism     0     1  
Rectal cancer recurrent     0     1  
Rectal neoplasm     0     1  
Skin cancer     0     1  
Skin ulcer     0     1  
Small cell lung cancer stage unspecified     0     1  
Sternal fracture     0     1  
Subdural haemorrhage     0     1  
Sudden death     0     1  
Thoracic vertebral fracture     0     1  
Thyroid cancer     0     1  
Vulval cancer     0     1  

No statistical analysis provided for Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up




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  Other Adverse Events


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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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