ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00379769
Recruitment Status : Completed
First Posted : September 22, 2006
Results First Posted : November 13, 2009
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Rosiglitazone
Drug: Sulfonylurea
Drug: Metformin
Enrollment 4447

Recruitment Details 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 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.
Arm/Group Title 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
Hide Arm/Group Description 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. 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. 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. 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. 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. 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.
Period Title: Main Study
Started 1117 1105 1103 1122 0 0
Completed 939 906 896 892 0 0
Not Completed 178 199 207 230 0 0
Reason Not Completed
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 Title: 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
Reason Not Completed
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.
Arm/Group Title 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
Hide Arm/Group Description 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. 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 1117 1105 1103 1122 4447
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1117 participants 1105 participants 1103 participants 1122 participants 4447 participants
57.0  (8.02) 57.2  (8.14) 59.8  (8.26) 59.7  (8.23) 58.4  (8.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1117 participants 1105 participants 1103 participants 1122 participants 4447 participants
Female
516
  46.2%
521
  47.1%
562
  51.0%
554
  49.4%
2153
  48.4%
Male
601
  53.8%
584
  52.9%
541
  49.0%
568
  50.6%
2294
  51.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1117 participants 1105 participants 1103 participants 1122 participants 4447 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
1.Primary Outcome
Title Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
321 323
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval 95%
0.85 to 1.16
Estimation Comments [Not Specified]
2.Primary Outcome
Title Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
139 160
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval 95%
0.68 to 1.08
Estimation Comments [Not Specified]
3.Primary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
181 188
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval 95%
0.78 to 1.17
Estimation Comments [Not Specified]
4.Primary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
186 191
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval 95%
0.79 to 1.18
Estimation Comments [Not Specified]
5.Primary Outcome
Title Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
88 96
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval 95%
0.68 to 1.21
Estimation Comments [Not Specified]
6.Primary Outcome
Title Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
88 96
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval 95%
0.68 to 1.21
Estimation Comments [Not Specified]
7.Primary Outcome
Title Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
68 60
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval 95%
0.80 to 1.59
Estimation Comments [Not Specified]
8.Primary Outcome
Title Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
72 62
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval 95%
0.82 to 1.62
Estimation Comments [Not Specified]
9.Primary Outcome
Title Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
50 63
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval 95%
0.54 to 1.14
Estimation Comments [Not Specified]
10.Primary Outcome
Title Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
53 64
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined RSG, Combined MET/SU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval 95%
0.57 to 1.18
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants With Cardiovascular Events and All-cause Deaths
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
12.Secondary Outcome
Title Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
13.Secondary Outcome
Title Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1117 1105 1103 1122
Measure Type: Number
Unit of Measure: partcipants
158 154 163 169
14.Secondary Outcome
Title Number of Participants With CV/Microvascular Events
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title Combined RSG Combined MET/SU
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
15.Secondary Outcome
Title Number of Participants With Glycaemic Failure Events
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1117 1105 1103 1122
Measure Type: Number
Unit of Measure: participants
281 451 365 424
16.Secondary Outcome
Title Number of Participants With Addition of Third Oral Agent/Switch to Insulin
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1117 1105 1103 1122
Measure Type: Number
Unit of Measure: participants
Participants with an event 295 183 344 171
First Event - Triple Therapy 257 7 296 6
First Event - Insulin 38 176 49 165
17.Secondary Outcome
Title The Number of Participants Starting Insulin at Any Time During the Study
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1117 1105 1103 1122
Measure Type: Number
Unit of Measure: participants
126 276 168 259
18.Secondary Outcome
Title Model Adjusted Change From Baseline in HbA1c at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1096 1079 1073 1079
Mean (Standard Error)
Unit of Measure: Percent
-0.14  (0.035) 0.17  (0.042) -0.24  (0.039) -0.10  (0.039)
19.Secondary Outcome
Title Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1095 1078 1074 1079
Mean (Standard Error)
Unit of Measure: mmol/L (millimoles/Liter)
-1.38  (0.073) -0.29  (0.090) -2.00  (0.085) -0.94  (0.094)
20.Secondary Outcome
Title Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 931 982 882 940
Mean (Standard Error)
Unit of Measure: picamoles/liter (pmol/L)
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)
21.Secondary Outcome
Title Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1117 1105 1103 1122
Measure Type: Number
Unit of Measure: participants
HbA1c Responders 265 208 235 180
FPG Responders 300 180 257 154
22.Secondary Outcome
Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 926 977 878 933
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
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)
23.Secondary Outcome
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1117 1105 1103 1122
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
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)
24.Secondary Outcome
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1117 1105 1103 1122
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
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)
25.Secondary Outcome
Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 949 1007 906 970
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
-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)
26.Secondary Outcome
Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 899 921 891 901
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
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)
27.Secondary Outcome
Title Model Adjusted Change From Baseline in Body Weight at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1096 1079 1073 1079
Mean (Standard Error)
Unit of Measure: kilograms
3.93  (0.263) -0.54  (0.192) 4.72  (0.235) -2.16  (0.179)
28.Secondary Outcome
Title Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1094 1077 1073 1078
Mean (95% Confidence Interval)
Unit of Measure: U/L (Units/Liter)
-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)
29.Secondary Outcome
Title Model Adjusted Change From Baseline in Waist Circumference at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 972 1032 926 994
Mean (Standard Error)
Unit of Measure: cm (centimeters)
2.70  (0.266) 0.65  (0.214) 3.00  (0.263) -0.60  (0.215)
30.Secondary Outcome
Title Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 1096 1079 1074 1079
Mean (Standard Error)
Unit of Measure: mmHg (millimeters of mercury)
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)
31.Secondary Outcome
Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 942 987 887 952
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
-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)
32.Secondary Outcome
Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 918 987 875 941
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
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)
33.Secondary Outcome
Title Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication
Arm/Group Title RSG in Addition to Background MET SU in Addition to Background MET RSG in Addition to Background SU MET in Addition to Background SU
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 931 991 882 939
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
-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)
34.Secondary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
35.Secondary Outcome
Title Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: 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
36.Secondary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
37.Secondary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: 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
38.Secondary Outcome
Title Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
39.Secondary Outcome
Title Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: 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
40.Secondary Outcome
Title Number of Participants With a Bone Fracture Event – Overall and by Gender: Main Study and Observational Follow-up Combined
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
Overall, n=2220, 2227 238 151
Male, n=1142, 1152 82 60
Female, n=1078, 1075 156 91
41.Secondary Outcome
Title Number of Participants With a Bone Fracture Event – Overall and by Gender: Observational Follow-up
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: participants
Overall, n=1280, 1250 64 37
Male, n=665, 635 25 11
Female, n=615, 615 39 26
42.Secondary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
43.Secondary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: 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
44.Secondary Outcome
Title Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
0 0
45.Secondary Outcome
Title Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
46.Secondary Outcome
Title Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: 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
47.Secondary Outcome
Title Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
48.Secondary Outcome
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
49.Secondary Outcome
Title Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: participants
Any event 238 151
Non-traumatic event 113 55
Traumatic event 110 77
Pathologic 1 4
Unknown 20 19
Data unavailable 9 3
50.Secondary Outcome
Title Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: participants
Any event 64 37
Non-traumatic event, 36 14
Traumatic event 24 17
Pathologic 1 2
Unknown 1 4
Data unavailable 3 1
51.Secondary Outcome
Title Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Analyses were performed by the original randomized treatment in the main RECORD study (referred to as Combined RSG and Combined MET/SU).
Arm/Group Title Combined RSG: Main Study and Observational Follow-up Combined MET/SU: Main Study and Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 2220 2227
Measure Type: Number
Unit of Measure: 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
52.Secondary Outcome
Title Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: 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
53.Secondary Outcome
Title Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Combined RSG: Observational Follow-up Combined MET/SU: Observational Follow-up
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 1280 1250
Measure Type: Number
Unit of Measure: 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
Time Frame In the RECORD study (RS), SAEs were collected from BL through End of Study (up to 7.5 years); non-serious AEs were collected only for the randomized treatment period. SAEs were collected from the end of the RS through the end of OFU (up to 4.0 years).
Adverse Event Reporting 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. Other than bone fractures (tabulated in the Outcome Measure Module), no non-serious AEs were collected.
 
Arm/Group Title 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
Hide Arm/Group Description 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. 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. 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. 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. 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. 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.
All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   424/1117 (37.96%)   428/1105 (38.73%)   427/1103 (38.71%)   431/1122 (38.41%)   99/1280 (7.73%)   76/1250 (6.08%) 
Blood and lymphatic system disorders             
Anaemia  1  8/1117 (0.72%)  2/1105 (0.18%)  4/1103 (0.36%)  5/1122 (0.45%)  1/1280 (0.08%)  0/1250 (0.00%) 
Iron Deficiency Anaemia  1  1/1117 (0.09%)  3/1105 (0.27%)  2/1103 (0.18%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Hypocoagulable State  1  1/1117 (0.09%)  0/1105 (0.00%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Thrombocytopenia  1  1/1117 (0.09%)  0/1105 (0.00%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Idiopathic Thrombocytopenic Purpura  1  0/1117 (0.00%)  1/1105 (0.09%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Autoimmune Thrombocytopenia  1  0/1117 (0.00%)  0/1105 (0.00%)  0/1103 (0.00%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Haemolytic Anaemia  1  0/1117 (0.00%)  0/1105 (0.00%)  0/1103 (0.00%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cardiac disorders             
Myocardial Infarction  1  25/1117 (2.24%)  22/1105 (1.99%)  29/1103 (2.63%)  23/1122 (2.05%)  0/1280 (0.00%)  1/1250 (0.08%) 
Cardiac Failure Congestive  1  25/1117 (2.24%)  18/1105 (1.63%)  23/1103 (2.09%)  13/1122 (1.16%)  0/1280 (0.00%)  0/1250 (0.00%) 
Angina Pectoris  1  23/1117 (2.06%)  18/1105 (1.63%)  23/1103 (2.09%)  19/1122 (1.69%)  0/1280 (0.00%)  0/1250 (0.00%) 
Angina Unstable  1  16/1117 (1.43%)  20/1105 (1.81%)  21/1103 (1.90%)  18/1122 (1.60%)  0/1280 (0.00%)  0/1250 (0.00%) 
Atrial Fibrillation  1  20/1117 (1.79%)  15/1105 (1.36%)  13/1103 (1.18%)  14/1122 (1.25%)  0/1280 (0.00%)  0/1250 (0.00%) 
Acute Myocardial Infarction  1  12/1117 (1.07%)  6/1105 (0.54%)  11/1103 (1.00%)  19/1122 (1.69%)  1/1280 (0.08%)  1/1250 (0.08%) 
Cardiac Failure  1  16/1117 (1.43%)  1/1105 (0.09%)  13/1103 (1.18%)  8/1122 (0.71%)  0/1280 (0.00%)  0/1250 (0.00%) 
Coronary Artery Disease  1  9/1117 (0.81%)  6/1105 (0.54%)  7/1103 (0.63%)  12/1122 (1.07%)  0/1280 (0.00%)  0/1250 (0.00%) 
Myocardial Ischaemia  1  7/1117 (0.63%)  5/1105 (0.45%)  7/1103 (0.63%)  5/1122 (0.45%)  0/1280 (0.00%)  0/1250 (0.00%) 
Coronary Artery Stenosis  1  4/1117 (0.36%)  8/1105 (0.72%)  5/1103 (0.45%)  7/1122 (0.62%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cardiac Failure Acute  1  3/1117 (0.27%)  2/1105 (0.18%)  3/1103 (0.27%)  3/1122 (0.27%)  1/1280 (0.08%)  0/1250 (0.00%) 
Arrythmia  1  1/1117 (0.09%)  4/1105 (0.36%)  2/1103 (0.18%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Bradycardia  1  1/1117 (0.09%)  3/1105 (0.27%)  1/1103 (0.09%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Acute Coronary Syndrome  1  3/1117 (0.27%)  0/1105 (0.00%)  0/1103 (0.00%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Arteriosclerosis Coronary Artery  1  2/1117 (0.18%)  1/1105 (0.09%)  0/1103 (0.00%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Tachycardia  1  2/1117 (0.18%)  1/1105 (0.09%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Atrioventricular Block Complete  1  1/1117 (0.09%)  2/1105 (0.18%)  0/1103 (0.00%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cardiac Arrest  1  1/1117 (0.09%)  2/1105 (0.18%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Aortic Valve Disease  1  2/1117 (0.18%)  0/1105 (0.00%)  0/1103 (0.00%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Sick Sinus Syndrome  1  2/1117 (0.18%)  0/1105 (0.00%)  1/1103 (0.09%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Atrial Flutter  1  1/1117 (0.09%)  1/1105 (0.09%)  1/1103 (0.09%)  4/1122 (0.36%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cardiac Disorder  1  1/1117 (0.09%)  1/1105 (0.09%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Silent Myocardial Infarction  1  1/1117 (0.09%)  1/1105 (0.09%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Mitral Valve Incompetence  1  0/1117 (0.00%)  2/1105 (0.18%)  0/1103 (0.00%)  1/1122 (0.09%)  0/1280 (0.00%)  0/1250 (0.00%) 
Atrial Tachycardia  1  1/1117 (0.09%)  0/1105 (0.00%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Atrioventricular Block Second Degree  1  1/1117 (0.09%)  0/1105 (0.00%)  2/1103 (0.18%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cardiac Failure Chronic  1  1/1117 (0.09%)  0/1105 (0.00%)  1/1103 (0.09%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cardiomegaly  1  1/1117 (0.09%)  0/1105 (0.00%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cardiovascular disorder  1  1/1117 (0.09%)  0/1105 (0.00%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Cor pulmonale  1  1/1117 (0.09%)  0/1105 (0.00%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Left Ventricular Failure  1  1/1117 (0.09%)  0/1105 (0.00%)  0/1103 (0.00%)  0/1122 (0.00%)  0/1280 (0.00%)  0/1250 (0.00%) 
Mitral Valve Disease  1  1/1117 (0.09%)