Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00379769
First received: September 21, 2006
Last updated: August 17, 2016
Last verified: August 2016
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 
Overall Participants Analyzed 
[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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information