ClinicalTrials.gov
ClinicalTrials.gov Menu

A Type 2 Diabetes Study of the Longer-Term Glycemic Effect of AVANDAMET vs. Metformin

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: NCT00386100
Recruitment Status : Completed
First Posted : October 11, 2006
Results First Posted : April 5, 2011
Last Update Posted : November 23, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Avandamet 6 mg/1500 mg (ttd)
Drug: Avandamet 4 mg/1000 mg (ttd)
Drug: Avandamet 2 mg/500 mg (ttd)
Drug: Avandamet 8 mg/ 2000 mg (ttd)
Drug: Metformin 500 mg (ttd)
Drug: Metformin 1000 mg (ttd)
Drug: Metformin 1500 mg (ttd)
Drug: Metformin 2000 mg (ttd)
Enrollment 688
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg. Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Period Title: Overall Study
Started 340 348
Completed 186 217
Not Completed 154 131
Reason Not Completed
Did not receive study medication             6             4
Adverse Event             15             25
Death             0             1
Insufficient therapeutic effect             30             6
Lost to Follow-up             29             29
Non-compliance             18             19
Protocol Violation             5             3
Withdrawal by Subject             32             31
Bone mass density (BMD) loss >6%             4             4
BMD <2.5             1             0
Consecutive elevated Hba1C             1             0
Visit 11 DXA showed excessive bone loss             0             1
Laboratory findings             1             0
Participant's concern due to CPK levels             1             0
Participant moving out of state             2             0
Excessive bone loss vs. baseline value             0             1
Didn't meet entry criteria             1             1
Participant's PCP wanted to stop drug             1             0
Osteoporosis findings on Visit 2 DXA             0             1
Bad metabolic control & patient security             1             0
Bone loss by DXA bone scan             1             0
DBP 93 mmHg at randomization             1             0
7.6% bone loss             1             0
Osteoporosis             0             1
Positive pregnancy test             1             3
Out of country for 5 months             1             0
Hb1Ac >8%             0             1
Participant randomized in error             1             0
Arm/Group Title Metformin Avandamet Total
Hide Arm/Group Description Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg. Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg. Total of all reporting groups
Overall Number of Baseline Participants 334 344 678
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 334 participants 344 participants 678 participants
50.7  (10.49) 51.5  (10.52) 51.1  (10.50)
[1]
Measure Description: The Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication, was used for all baseline characteristics.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 334 participants 344 participants 678 participants
Female
158
  47.3%
160
  46.5%
318
  46.9%
Male
176
  52.7%
184
  53.5%
360
  53.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 334 participants 344 participants 678 participants
African America/African 13 17 30
American Indian or Alaskan Native 3 7 10
Asian – Central/South Asian 23 22 45
Asian – East Asian 44 51 95
Asian – Japanese 0 1 1
Asian – South East Asian 48 48 96
White – Arabic/North African 4 3 7
White – White/Caucasian/European 185 183 368
Mixed Race 5 5 10
Not Specified 9 7 16
Duration of Diabetes   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 334 participants 344 participants 678 participants
2.570  (3.2671) 2.293  (3.0774) 2.429  (3.1729)
[1]
Measure Description: The Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication, was used for all baseline characteristics.
1.Primary Outcome
Title Change From Baseline in HbA1c at Week 80
Hide Description Blood was taken for serum HbA1c measurements. Change from baseline was calculated as the Week 80 value minus the baseline value. Last observation carried forward (LOCF) was not used for this analysis.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value. Only evaluable participants, defined as the number of participants with a baseline and at least one post baseline assessment, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 294 301
Mean (Standard Error)
Unit of Measure: percent change
Baseline 8.64  (0.053) 8.64  (0.055)
Change from Baseline -1.36  (0.073) -1.85  (0.070)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No adjustment for multiple comparisons
Method Repeated measures analysis
Comments Repeated measures analysis with terms for baseline, region, treatment, gender, time, and treatment by time interaction
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.69 to -0.30
Estimation Comments AVM mean change from baseline minus MET mean change from baseline based on repeated measures analysis model
2.Secondary Outcome
Title Mean Change From Baseline in HbA1c at Week 80
Hide Description Blood was taken for serum Hb1AC measurements. Change from baseline was calculated as the Week 80 value minus the baseline value, with LOCF from Week 32 for withdrawn participants or missing values.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF: a subset of the ITT Population with LOCF starting at Week 32. Only participants with assessment(s) at Week 32 or later were included in this population. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 258 265
Mean (Standard Deviation)
Unit of Measure: percent change
Baseline 8.59  (0.898) 8.66  (0.954)
Change from Baseline -1.42  (0.070) -1.91  (0.069)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No adjustment for multiple comparisons
Method ANCOVA
Comments ANCOVA with terms for treatment, region, gender, and baseline value with LOCF from Week 32 for withdrawn participants or missing values
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-0.669 to -0.305
Estimation Comments AVM mean change from baseline minus MET mean change from baseline based on ANCOVA model
3.Secondary Outcome
Title Number of Participants Achieving HbA1c <=6.5% and <7% at Week 80
Hide Description Blood was taken for serum Hb1AC measurements. Hb1AC responders were described as participants having achieved Hb1AC <=6% and <7% at Week 80 with LOCF from Week 32.
Time Frame Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 258 265
Measure Type: Number
Unit of Measure: participants
<=6.5% 97 128
<7% 133 184
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
Comments Hb1AC <= 6.5%
Method Regression, Logistic
Comments Logistic reggression with terms for treatment, region, gender, and baseline Hb1AC with LOCF from Week 32.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
1.18 to 2.46
Estimation Comments Odds of having an HbA1c <= 6.5% at Week 80 on Avandamet compared to Metformin.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hb1AC < 7%
Method Regression, Logistic
Comments Logistic reggression with terms for treatment, region, gender, and baseline Hb1AC with LOCF from Week 32
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.59
Confidence Interval (2-Sided) 95%
1.75 to 3.81
Estimation Comments Odds of having an HbA1c <7% at Week 80 on Avandamet compared to Metformin
4.Secondary Outcome
Title Change in Fasting Plasma Glucose (FPG) From Baseline at Week 80
Hide Description Blood was taken for serum FPG measurements. Change from baseline was calculated as the Week 80 value minus the baseline value.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only evaluable participants, defined as the number of participants with a baseline and at least one post baseline assessment, were analyzed. Last observation carried forward (LOCF) was not used for this analysis.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 319 332
Mean (Standard Error)
Unit of Measure: millimoles per Liter (mmol/l)
Baseline 10.52  (0.184) 10.17  (0.162)
Change from Baseline -2.25  (0.147) -3.41  (0.139)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures analysis
Comments Terms for baseline, region, treatment, pre-screening Hb1Ac strata, gender, time, and treatment by time interaction
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.15
Confidence Interval 95%
-1.54 to -0.77
Estimation Comments AVM mean change from baseline minus MET mean change from baseline based on repeated measures analysis model
5.Secondary Outcome
Title Change From Baseline in FPG at Week 80
Hide Description Blood was taken for serum FPG measurements. Change from baseline was calculated as the Week 80 value minus the baseline value with LOCF from Week 32 for withdrawn participants or missing values.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 258 265
Mean (Standard Deviation)
Unit of Measure: mmol/l
Baseline 10.37  (3.268) 10.13  (2.927)
Change from Baseline -2.53  (3.165) -3.39  (2.908)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No adjustment for multiple comparisons
Method ANCOVA
Comments Terms for treatment, region, gender, pre-screening Hb1Ac strata, and baseline with LOCF from Week 32 for withdrawn participants or missing values
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.07
Confidence Interval (2-Sided) 95%
-1.425 to -0.710
Estimation Comments AVM mean change from baseline minus MET mean change from baseline based on ANCOVA model
6.Secondary Outcome
Title Number of Participants Achieving FPG <=6 mmol/L (110 mg/dL) and <=7 mmol/L (126 mg/dL) at Week 80
Hide Description Blood was taken for serum FPG measurements. FPG responders were described as participants having achieved FPG <=6 mmol/L (110 mg/dL) and <7 mmol/L (126 mg/dL) Hb1AC at Week 80 with LOCF from Week 32.
Time Frame Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 258 265
Measure Type: Number
Unit of Measure: participants
FPG <=6.1 mmol/l 31 83
FPG <=7.0 mmol/l 55 133
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments FPG <=6.1 mmol/l
Method Regression, Logistic
Comments Terms for treatment, region, gender, pre-screening Hb1Ac strata, and baseline with LOCF from Week 32.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.47
Confidence Interval (2-Sided) 95%
2.94 to 6.81
Estimation Comments Odds of having an FPG <=6.1 mmol/l at Week 80 on Avandamet compared to Metformin
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments FPG <=7 mmol/l
Method Regression, Logistic
Comments Terms for treatment, region, gender, pre-screening Hb1Ac, and baseline with LOCF from Week 32.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.33
Confidence Interval (2-Sided) 95%
2.25 to 4.92
Estimation Comments Odds of having an FPG <=7 mmol/l at Week 80 on Avandamet compared to Metformin
7.Secondary Outcome
Title Number of Participants Achieving Treatment Failure
Hide Description Treatment failure was defined as an HbA1c level >= 7% after Week 32 or withdrawal due to insufficient therapeutic effect (ITE) at any time.
Time Frame Randomization to treatment failure (up to Week 80)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only evaluable participants, defined as the number of subjects with a baseline and at least one post baseline assessment, were analyzed. Last observation carried forward (LOCF) was not used for this analysis
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 319 332
Measure Type: Number
Unit of Measure: participants
156 114
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments Cox proportional hazard regression with terms for treatment, region, baseline Hb1Ac strata, and gender
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.45 to 0.74
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
Hide Description Blood was taken for measurement of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. Percent change from baseline at Week 80 was based on log transformed data. Geometric mean, GM; standard error, SE. n is the number of evaluable participants, which is the number of participants with a value at baseline and at the specified visit for the parameter of interest.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 evaluable population with LOCF from Week 32. n is the number of evaluable participants, which is defined as the number of participants with a value at baseline and at the specified visit for the parameter of interest.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 258 265
Measure Type: Number
Unit of Measure: percent change
% change + SE, Total cholesterol, n=258, 265 -1.615 4.218
% change, Total cholesterol, n=258, 265 -2.89 2.91
% change - SE, Total cholesterol, n=258, 265 -4.140 1.614
% change + SE, LDL cholesterol, n=248, 252 -4.933 3.304
% change, LDL cholesterol, n=248, 252 -7.11 0.98
% change - SE, LDL cholesterol, n=248, 252 -9.228 -1.286
% change + SE, HDL cholesterol, n=258, 265 6.761 9.483
% change, HDL cholesterol, n=258, 265 5.60 8.324
% change - SE, HDL cholesterol, n=258, 265 4.453 7.179
% change + SE, triglycerides, n=258, 265 -2.696 -2.042
% change, triglycerides, n=258, 265 -5.330 -4.627
% change - SE, triglycerides, n=258, 265 -7.893 -7.143
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments Total cholesterol. No adjustment for multiple comparisons. Log transformed
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 5.97
Confidence Interval (2-Sided) 95%
2.522 to 9.526
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.056
Comments LDL cholesterol. No adjustment for multiple comparisons. Log transformed
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 8.71
Confidence Interval (2-Sided) 95%
2.486 to 15.304
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments HDL cholesterol. No adjustment for multiple comparison. Log transformed.
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 2.580
Confidence Interval (2-Sided) 95%
-0.232 to 5.470
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.835
Comments Triglycerides. No adjustment for multiple comparisons. Log transformed.
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 0.743
Confidence Interval (2-Sided) 95%
-6.056 to 8.035
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent Change From Baseline in Adiponectin at Week 80 (United States [US] and Mexico Subset of Participants )
Hide Description Blood was taken for measurement of adiponectin. Percent change from baseline at Week 80 was based on log transformed data. This outcome measure was analyzed for a subset of participants in the US and Mexico only.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF for US and Mexico subset. Only evaluable participants, defined as the number of participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 91 96
Measure Type: Number
Unit of Measure: percent change
Percent change from baseline + SE 18.58 139.28
Percent change from baseline 12.96 128.44
Percent change from baseline - SE 7.61 118.10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments No adjustment for multiple comparisons. Log transformed.
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 102.24
Confidence Interval (2-Sided) 95%
79.23 to 128.19
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline in C-reactive Protein (CRP) at Week 80 (US and Mexico Subset of Participants)
Hide Description Blood was taken for measurement of CRP. Percent change from baseline at Week 80 was based on log transformed data. This outcome measure was analyzed for a subset of participants in the US and Mexico only.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF for US and Mexico subset. Only evaluable participants, defined as the number of participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 92 95
Measure Type: Number
Unit of Measure: percent change
Percent change from baseline + SE -6.49 14.28
Percent change from baseline -10.63 -17.96
Percent change from baseline - SE -14.59 -21.49
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1380
Comments No adjustment for multiple comparisons. Log transformed.
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value -8.20
Confidence Interval (2-Sided) 95%
-18.04 to 2.82
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percent Change in Free Fatty Acids (FFA) From Baseline at Week 80 (US and Mexico Subset of Participants).
Hide Description Blood was taken for measurement of FFA. Percent change from baseline at Week 80 was based on log transformed data. This outcome measure was analyzed for a subset of participants in the US and Mexico only.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF for US and Mexico subset. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 92 95
Measure Type: Number
Unit of Measure: percent change
Percent change from baseline + SE 14.353 1.267
Percent change from baseline 9.40 -2.97
Percent change from baseline - SE 4.657 -7.028
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0342
Comments No adjustment for multiple comparisons. Log transformed.
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value -11.308
Confidence Interval (2-Sided) 95%
-20.617 to -0.899
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change in Fasting Insulin From Baseline at Week 80 (US and Mexico Subset of Participants)
Hide Description Blood was taken for fasting insulin measurements. Change from baseline was calculated as the Week 80 value minus the baseline value, with LOCF from Week 32 for withdrawn participants or missing values. This outcome measure was analyzed for a subset of participants in the US and Mexico only.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF for US and Mexico subset. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 92 97
Mean (Standard Error)
Unit of Measure: picomoles per Liter (pmol/l)
-1.5  (9.18) -35.2  (8.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0042
Comments No adjustment for multiple comparisons.
Method ANCOVA
Comments ANCOVA with terms for treatment, region, gender, pre-screening HbA1c strata, and baseline.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -33.7
Confidence Interval (2-Sided) 95%
-56.666 to -0.99
Estimation Comments AVM mean change from baseline minus MET mean change from baseline based on ANCOVA model
13.Secondary Outcome
Title Change in C-peptide From Baseline at Week 80 (US and Mexico Subset of Participants)
Hide Description Blood was taken for C-peptide measurements. Change from baseline was calculated as the Week 80 value minus the baseline value with LOCF from Week 32 for withdrawn participants or missing values. This outcome measure was analyzed for a subset of participants in the US and Mexico only.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF for US and Mexico subset. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 92 95
Mean (Standard Error)
Unit of Measure: mmol/l
-0.244  (0.0518) -0.473  (0.0502)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments No adjustment for multiple comparisons.
Method ANCOVA
Comments ANCOVA with terms for treatment, region, gender, pre-screening HbA1c strata, and baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.229
Confidence Interval (2-Sided) 95%
-0.359 to -0.099
Estimation Comments AVM mean change from baseline minus MET mean change from baseline based on ANCOVA model
14.Secondary Outcome
Title Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)
Hide Description Blood was taken for measurement of homeostasis model assessment for insulin sensitivity (HOMA-S) and beta-cell function (HOMA-B). Percent change from baseline at Week 80 was based on log transformed data. This outcome measure was analyzed for a subset of participants in the US and Mexico only. GM, geometric mean; SE, standard error.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF for US and Mexico subset. Only evaluable participants, defined as participants with a value at baseline and at the specified visit for the parameter of interest, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 91 96
Measure Type: Number
Unit of Measure: percent change
Percent change HOMA-B + SE 88.25 92.32
Percent change HOMA-B 78.85 83.14
Percent change HOMA-B - SE 69.92 74.39
Percent change HOMA-S + SE 25.13 63.67
Percent change HOMA-S 18.65 55.58
Percent change HOMA-S - SE 12.49 47.91
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7148
Comments HOMA-B. Log transformed.
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 2.40
Confidence Interval (2-Sided) 95%
-9.87 to 16.34
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments HOMA-S. Log transformed.
Method ANCOVA
Comments ANCOVA with log (value) minus log (baseline [BL]) as dependent variable. Terms for treatment, region, gender, pre-screening HbA1c strata, and log (BL)
Method of Estimation Estimation Parameter percent difference from metformin
Estimated Value 31.14
Confidence Interval (2-Sided) 95%
14.82 to 49.78
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Slope of Delta-cell Function as Estimated by the Ratio deltaI/deltaG
Hide Description The ratio Delta I/Delta G is calculated based on the oral glucose tolerance test (OGTT), where Delta I = (30 minute immunoreactive insulin minus 0 minute immunoreactive insulin) and Delta G = (30 minute plasma glucose minus 0 minute plasma glucose). The 0 minute values are fasting insulin and glucose; the 30 minute values are taken 30 minutes after the oral glucose challenge. This outcome measure was analyzed for a subset of participants in the US and Mexico only.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 32 Evaluable Population with LOCF. Only evaluable participants, defined as participants from US and Mexico sites with a value at baseline and at the specified visit, were analyzed.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 82 89
Mean (Standard Error)
Unit of Measure: ratio
-86.23  (59.706) -5.38  (55.229)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.319
Comments [Not Specified]
Method Repeated measures analysis
Comments Repeated measures analysis with terms for baseline, region, treatment, gender, pre-screening Hb1AC, time, and treatment by time interaction
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 80.85
Confidence Interval (2-Sided) 95%
-79.035 to 240.744
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Number of Participants at Final Dose Level
Hide Description [Not Specified]
Time Frame Baseline to Week 80 or withdrawal
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population. This population consisted of all participants who were randomized and received at least one dose of the study medication.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 334 344
Measure Type: Number
Unit of Measure: participants
Dose level 1 AVM 4 mg/500 mg, MET 500 mg 17 19
Dose level 2 AVM 4 mg/1000 mg, MET 1000 mg 16 18
Dose level 3 AVM 6 mg/1500 mg, MET 1500 mg 27 34
Dose level 4 AVM 8 mg/2000 mg, MET 2000 mg 236 242
17.Secondary Outcome
Title Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Hide Description BMD was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD at a given timepoint was defined at the participant level by the following formula: percent change = (BMD at given week minus BMD at baseline)/BMD at baseline x 100%. This outcome measure was analyzed for a subset of participants in the bone study only.
Time Frame Baseline and Weeks 20, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with BMD assessment(s) at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 87 87
Mean (Standard Error)
Unit of Measure: percent change
Overall population, Week 80, n=87, 87 -2.1  (0.54) 0.1  (0.54)
Overall population, Week 56, n=87, 87 -1.4  (0.45) 0.3  (0.44)
Overall population, Week 20, n=87, 87 -0.5  (0.41) 0.5  (0.40)
Male population, Week 80, n=38, 43 -0.7  (0.81) 1.0  (0.90)
Male population, Week 56, n=38, 43 -0.2  (0.61) 0.7  (0.68)
Male population, Week 20, n=38, 43 -0.1  (0.63) -0.2  (0.71)
Female population, Week 80, n=49, 44 -2.7  (0.77) 0.2  (0.75)
Female population, Week 56, n=49, 44 -2.0  (0.70) 0.3  (0.68)
Female population, Week 20, n=49, 44 -0.9  (0.52) 1.2  (0.51)
Premenopausal population, Week 80, n=21, 14 -2.4  (1.01) -0.7  (1.03)
Premenopausal population, Week 56, n=21, 14 -0.8  (0.88) 0.2  (0.90)
Premenopausal population, Week 20, n=21, 14 0.2  (0.75) 0.5  (0.77)
Postmenopausal population, Week 80, n=28, 30 -3.3  (1.22) 0  (1.16)
Postmenopausal population, Week 56, n=28, 30 -2.7  (1.09) -0.1  (1.04)
Postmenopausal population, Week 20, n=28, 30 -1.4  (0.73) -1.1  (0.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments Overall population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-3.5 to -0.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments Overall population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-2.7 to -0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0308
Comments Overall population, Week 20. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.0 to -0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0954
Comments Male population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-3.7 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments Female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-4.7 to -1.2
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments Female population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-3.9 to -0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments Female population, Week 20. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-3.3 to -1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2363
Comments Premenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-4.6 to 1.2
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0161
Comments Postmenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-5.9 to -0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0338
Comments Postmenopausal female population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-4.9 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments Postmenopausal female population, Week 20. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-4.1 to -1.0
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Hide Description BMD was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD at a given timepoint was defined at the participant level by the following formula: percent change = (BMD at given week minus BMD at baseline)/BMD at baseline x 100. This outcome measure was analyzed for a subset of participants in the bone study only.
Time Frame Baseline and Weeks 20, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with BMD assessment(s) at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 87 87
Mean (Standard Error)
Unit of Measure: percent change
Overall population, Week 80, n=87, 87 0.0  (0.35) -1.5  (0.35)
Overall population, Week 56, n=87, 87 -0.2  (0.31) -1.2  (0.32)
Overall population, Week 20, n=87, 87 0.2  (0.24) -0.4  (0.24)
Male population, Week 80, n=38, 43 0.3  (0.46) -1.0  (0.41)
Male population, Week 56, n=38, 43 0.2  (0.41) -0.8  (0.37)
Male population, Week 20, n=38, 43 0.5  (0.35) -0.3  (0.31)
Female population, Week 80, n=49, 44 0.0  (0.60) -1.8  (0.61)
Female population, Week 56, n=49, 44 -0.2  (0.52) -1.4  (0.54)
Female population, Week 20, n=49, 44 -0.3  (0.37) -0.6  (0.38)
Premenopausal population, Week 80, n=21, 14 1.3  (0.71) -0.9  (0.69)
Premenopausal population, Week 56, n=21, 14 0.8  (0.69) -1.6  (0.67)
Premenopausal population, Week 20, n=21, 14 0.3  (0.48) 0.0  (0.47)
Postmenopausal population, Week 80, n=28, 30 -0.9  (0.97) -2.3  (1.02)
Postmenopausal population, Week 56, n=28, 30 -1.1  (0.81) -1.5  (0.85)
Postmenopausal population, Week 20, n=28, 30 -0.4  (0.57) -0.6  (0.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments Overall population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.3 to -0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0110
Comments Overall population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.7 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0618
Comments Overall population, Week 20. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.1 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0110
Comments Male population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.3 to -0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0272
Comments Male population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.9 to -0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0337
Comments Male population, Week 20. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-1.6 to -0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0152
Comments Female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-3.1 to -0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0570
Comments Female population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.4 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0296
Comments Premenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-4.3 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0155
Comments Premenopausal female population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.4 to -0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5870
Comments Premenopausal female population, Week 20. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.7 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1854
Comments Postmenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.6 to 0.7
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Hide Description BMD was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD at a given timepoint was defined at the participant level by the following formula: percent change = (BMD at given week minus BMD at baseline)/BMD at baseline x 100. This outcome measure was analyzed for a subset of participants in the bone study only.
Time Frame Baseline and Weeks 20, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with BMD assessment(s) at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 87 87
Mean (Standard Error)
Unit of Measure: percent change
Overall population, Week 80, n=87, 87 -0.1  (0.54) -2.1  (0.55)
Overall population, Week 56, n=87, 87 -0.2  (0.49) -1.7  (0.49)
Overall population, Week 20, n=87, 87 0.1  (0.35) -0.6  (0.34)
Male population, Week 80, n=38, 43 1.1  (0.69) -0.4  (0.61)
Male population, Week 56, n=38, 43 0.9  (0.67) -0.5  (0.60)
Male population, Week 20, n=38, 43 0.7  (0.55) -0.2  (0.48)
Female population, Week 80, n=49, 44 -0.2  (0.93) -2.6  (0.96)
Female population, Week 56, n=49, 44 -0.3  (0.80) -2.1  (0.82)
Female population, Week 20, n=49, 44 -0.2  (0.52) -0.8  (0.53)
Premenopausal population, Week 80, n=21, 14 1.7  (1.18) -1.4  (1.12)
Premenopausal population, Week 56, n=21, 14 0.3  (0.94) -2.6  (0.89)
Premenopausal population, Week 20, n=21, 14 0.0  (0.71) 0.0  (0.67)
Postmenopausal population, Week 80, n=28, 30 -1.1  (1.45) -3.6  (1.53)
Postmenopausal population, Week 56, n=28, 30 -1.1  (1.25) -2.2  (1.31)
Postmenopausal population, Week 20, n=28, 30 -0.3  (0.76) -1.0  (0.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments Overall population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.2 to -0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0134
Comments Overall population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.7 to -0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0967
Comments Overall population, Week 20. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.5 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0512
Comments Male population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.0 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0330
Comments Female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.6 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0547
Comments Female population, Week 56. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.7 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0613
Comments Premenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-6.3 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1369
Comments Postmenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-3.9 to 1.7
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Hide Description BMD was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD at a given timepoint was defined at the participant level by the following formula: percent change = (BMD at given week minus BMD at baseline)/BMD at baseline x 100. This outcome measure was analyzed for a subset of participants in the bone study only.
Time Frame Baseline and Weeks 20, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with BMD assessment(s) at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 87 87
Mean (Standard Error)
Unit of Measure: percent change
Overall population, Week 80, n=87, 87 -0.7  (0.39) -1.4  (0.39)
Overall population, Week 56, n=87, 87 -0.7  (0.39) -0.8  (0.39)
Overall population, Week 20, n=87, 87 -0.1  (0.36) -0.2  (0.36)
Male population, Week 80, n=38, 43 -1.4  (0.66) -2.2  (0.59)
Male population, Week 56, n=38, 43 -0.7  (0.64) -1.3  (0.57)
Male population, Week 20, n=38, 43 -0.4  (0.60) -0.7  (0.53)
Female population, Week 80, n=49, 44 -0.3  (0.56) -1.2  (0.57)
Female population, Week 56, n=49, 44 -0.6  (0.55) -0.5  (0.56)
Female population, Week 20, n=49, 44 -0.4  (0.49) -0.2  (0.50)
Premenopausal population, Week 80, n=21, 14 0.9  (0.73) -0.3  (0.68)
Premenopausal population, Week 56, n=21, 14 -0.1  (0.96) -0.4  (0.89)
Premenopausal population, Week 20, n=21, 14 0.9  (0.83) -0.3  (0.77)
Postmenopausal population, Week 80, n=28, 30 -1.3  (0.87) -2.1  (0.91)
Postmenopausal population, Week 56, n=28, 30 -1.2  (0.81) -0.7  (0.85)
Postmenopausal population, Week 20, n=28, 30 -1.1  (0.71) -0.4  (0.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1260
Comments Overall population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.7 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3117
Comments Male population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-2.2 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1776
Comments Female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.2 to 0.4
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2259
Comments Premenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-3.2 to 0.8
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3840
Comments postmenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.8 to 1.1
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Hide Description BMD was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD at a given timepoint was defined at the participant level by the following formula: percent change = (BMD at given week minus BMD at baseline)/BMD at baseline x 100. This outcome measure was analyzed for a subset of participants in the bone study only.
Time Frame Baseline and Weeks 20, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with BMD assessment(s) at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 87 87
Mean (Standard Error)
Unit of Measure: percent change
Overall population, Week 80, n=87, 87 0.3  (0.63) -0.1  (0.66)
Overall population, Week 56, n=87, 87 0.5  (0.55) 0.5  (0.58)
Overall population, Week 20, n=87, 87 1.2  (0.58) 0.9  (0.61)
Male population, Week 80, n=38, 43 0.4  (0.84) -0.6  (0.82)
Male population, Week 56, n=38, 43 0.7  (0.73) 0.4  (0.71)
Male population, Week 20, n=38, 43 1.5  (0.75) 0.2  (0.73)
Female population, Week 80, n=49, 44 0.1  (1.00) 0.1  (1.07)
Female population, Week 56, n=49, 44 0.6  (0.87) 0.7  (0.93)
Female population, Week 20, n=49, 44 0.6  (0.94) 1.1  (0.99)
Premenopausal population, Week 80, n=21, 14 1.1  (1.51) -0.3  (1.44)
Premenopausal population, Week 56, n=21, 14 2.2  (1.37) -0.6  (1.30)
Premenopausal population, Week 20, n=21, 14 2.6  (1.51) 0.7  (1.40)
Postmenopausal population, Week 80, n=28, 30 -0.5  (1.61) -0.2  (1.76)
Postmenopausal population, Week 56, n=28, 30 -0.3  (1.34) 0.8  (1.46)
Postmenopausal population, Week 20, n=28, 30 0.5  (1.36) 1.3  (1.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6102
Comments Overall population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.9 to 1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3445
Comments Male population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.9 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9735
Comments Female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-2.4 to 2.3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4861
Comments Premenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-5.8 to 2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8770
Comments Postmenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-3.5 to 4.0
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Hide Description BMD was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD at a given timepoint was defined at the participant level by the following formula: percent change = (BMD at given week minus BMD at baseline)/BMD at baseline x 100. This outcome measure was analyzed for a subset of participants in the bone study only.
Time Frame Baseline and Weeks 20, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with BMD assessment(s) at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 87 87
Mean (Standard Error)
Unit of Measure: percent change
Overall population, Week 80, n=87, 87 1.1  (0.64) 1.1  (0.64)
Overall population, Week 56, n=87, 87 1.3  (0.63) -0.1  (0.63)
Overall population, Week 20, n=87, 87 0.0  (0.37) 0.5  (0.37)
Male population, Week 80, n=38, 43 0.3  (0.43) 0.5  (0.38)
Male population, Week 56, n=38, 43 0.5  (0.41) 0.5  (0.37)
Male population, Week 20, n=38, 43 0.2  (0.43) 0.5  (0.38)
Female population, Week 80, n=49, 44 2.0  (1.00) 1.0  (1.01)
Female population, Week 56, n=49, 44 1.9  (1.03) 1.2  (1.04)
Female population, Week 20, n=49, 44 -0.2  (0.56) 0.5  (0.57)
Premenopausal population, Week 80, n=21, 14 5.3  (2.26) -0.2  (2.73)
Premenopausal population, Week 56, n=21, 14 5.2  (2.42) -1.0  (2.94)
Premenopausal population, Week 20, n=21, 14 -0.2  (1.38) 0.3  (1.66)
Postmenopausal population, Week 80, n=28, 30 0.2  (0.56) -0.4  (0.67)
Postmenopausal population, Week 56, n=28, 30 -0.2  (0.49) -0.6  (0.58)
Postmenopausal population, Week 20, n=28, 30 -0.2  (0.45) 0.1  (0.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7015
Comments Overall population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.5 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6767
Comments Male population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.7 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4199
Comments Female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-3.4 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2526
Comments Premenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-16.4 to 5.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4153
Comments postmenopausal female population, Week 80. No adjustment for multiple comparisons. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.8 to 0.8
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Hide Description Blood was taken for measurement of serum calcium. Percent change from baseline was based on log transformed data. Geometric mean, GM; standard error, SE. This outcome measure was analyzed for a subset of participants in the bone study only. n is the number of evaluable participants, which is the number of participants with a value at baseline and at the specified visit for the parameter of interest.
Time Frame Baseline and Weeks 12, 32, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with serum calcium measurements at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 79 79
Measure Type: Number
Unit of Measure: percent change
Wk80 % change + SE, overall n= 79, 79 0.929 1.104
Wk80 % change, overall n=79, 79 0.424 0.592
Wk80 % change - SE, overall n= 79, 79 -0.079 0.083
Wk56 % change + SE, overall n= 79, 79 1.098 1.313
Wk56 % change, overall n= 79, 79 0.527 0.735
Wk56 % change - SE, overall n 79, 79 -0.040 0.160
Wk32 % change + SE, overall n=78, 77 0.136 -0.735
Wk32 % change, overall n= 78, 77 -0.316 -1.204
Wk32 % change - SE, overall n 78, 79 -0.766 -1.607
Wk12 % change + SE, overall n=81, 78 0.568 -0.315
Wk12 % change, overall n= 81, 78 0.123 -0.767
Wk12 % change - SE, overall n 81, 78 -0.320 -1.216
Wk80 % change + SE, males n=34, 39 0.8777 1.551
Wk80 % change, males n= 34, 39 0.071 0.817
Wk80 % change - SE, males n 34, 39 -0.728 0.877
Wk56 % change + SE, males n=34, 39 1.304 1.092
Wk56 % change, males n= 34, 39 0.646 0.498
Wk56 % change - SE, males n 34, 39 -0.009 -0.094
Wk32 % change + SE, males n=33, 39 -0.538 -0.585
Wk32 % change, males n= 33, 39 -1.281 -1.254
Wk32 % change - SE, males n 33,39 -2.019 -1.919
Wk12 % change + SE, males n=37, 40 1.410 0.543
Wk12 % change, males n= 37, 40 0.656 -0.147
Wk12 % change - SE, males n 37, 40 -0.091 -0.833
Wk80 % change + SE, females n= 45, 40 1.508 1.049
Wk80 % change, females n=45, 40 0.735 0.279
Wk80 % change - SE, females n= 45, 40 -0.033 -0.484
Wk56 % change + SE, females n= 45, 40 1.692 1.884
Wk56 % change, females n=45, 40 0.720 0.911
Wk56 % change - SE, females n= 45, 40 -0.242 -0.053
Wk32 % change + SE, females n= 45, 38 0.637 -0.653
Wk32 % change, females n=45, 38 0.038 -1.293
Wk32 % change - SE, females n= 45, 38 -0.557 -1.930
Wk12 % change + SE, females n= 44, 38 0.715 -0.425
Wk12 % change, females n=44, 38 0.055 -1.081
Wk12 % change - SE, females n= 44, 38 -0.600 -1.733
Wk80 % change + SE, premenopausal females n=19, 14 1.429 0.704
Wk80 % change, premenopausal females n= 19, 14 0.531 -0.111
Wk80 % change - SE, premenopausal females n 19, 14 -0.359 -0.918
Wk56 % change + SE, premenopausal females n=19, 14 2.091 2.334
Wk56 % change, premenopausal females n= 19, 14 0.960 1.298
Wk56 % change - SE, premenopausal females n 19, 14 -0.159 0.273
Wk32 % change + SE, premenopausal females n=19, 13 1.074 -0.650
Wk32 % change, premenopausal females n= 19, 13 0.070 -1.679
Wk32 % change - SE, premenopausal females n 19, 13 -0.923 -2.698
Wk12 % change + SE, premenopausal females n=19, 13 0.420 -0.218
Wk12 % change, premenopausal females n= 19, 13 -0.657 -1.280
Wk12 % change - SE, premenopausal females n 19, 13 -1.722 -2.330
Wk80 % change+ SE, postmenopausal females n=26, 26 2.019 1.915
Wk80 % change, postmenopausal females n=26, 26 0.760 0.604
Wk80% change - SE, postmenopausal females n=26, 26 -0.484 -0.690
Wk56 % change+ SE, postmenopausal females n=26, 26 2.181 2.691
Wk56 % change, postmenopausal females n=26, 26 0.560 0.993
Wk56% change - SE, postmenopausal females n=26, 26 -1.035 -0.677
Wk32 % change+ SE, postmenopausal females n=26, 25 0.844 -0.535
Wk32 % change, postmenopausal females n=26, 25 0.056 -1.360
Wk32% change - SE, postmenopausal females n=26, 25 -0.726 -2.178
Wk12 % change+ SE, postmenopausal females n=25, 25 0.844 -1.163
Wk12 % change, postmenopausal females n=25, 25 -0.042 -2.074
Wk12% change - SE, postmenopausal females n=25, 25 -0.921 -2.976
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7895
Comments Overall population, Week 80. Log transformed. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 0.168
Confidence Interval (2-Sided) 95%
-1.066 to 1.417
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4155
Comments Males, Week 80. Log transformed. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 0.745
Confidence Interval (2-Sided) 95%
-1.064 to 2.587
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6223
Comments Females, Week 80. Log transformed. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value -0.452
Confidence Interval (2-Sided) 95%
-2.253 to 1.382
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5908
Comments Premenopausal females, Week 80. Log transformed. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value -0.638
Confidence Interval (2-Sided) 95%
-3.043 to 1.826
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9154
Comments Postmenopausal females, Week 80. Log transformed. If the p value was significant at Week 80 a comparison was done at Week 56; if it was significant at Weeks 80 and 56, a comparison was done at Week 20.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value -0.155
Confidence Interval (2-Sided) 95%
-3.037 to 2.814
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Hide Description Blood was taken for measurement of intact parathyroid hormone. Percent change from baseline was based on log transformed data. Standard error, SE; Wk, Week; %, percent. This outcome measure was analyzed for a subset of participants in the bone study only. n is the number of evaluable participants, which is the number of participants with a value at baseline and at the specified visit for the parameter of interest.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with intact parathyroid hormone measurements at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 45 38
Measure Type: Number
Unit of Measure: percent change
Wk80 % change + SE, overall n= 45, 38 -1.296 0.843
Wk80 % change, overall n=45, 38 -7.634 -6.279
Wk80 % change - SE, overall n= 45, 38 -13.565 -12.898
Wk80 % change + SE, males n=16, 21 -1.160 -2.619
Wk80 % change, males n= 16, 21 -9.238 -8.941
Wk80 % change - SE, males n=16, 21 -16.655 -14.852
Wk80 % change + SE, females n= 30, 22 4.662 11.166
Wk80 % change, females n=30, 22 -4.608 -1.759
Wk 80 % change - SE, females n= 30, 22 -13.056 -13.182
Wk80 % change + SE, premenopausal females n=13, 7 14.295 24.396
Wk80 % change, premenopausal females n= 13, 7 -7.686 -0.126
Wk80 % change - SE, premenopausal females n=13, 7 -25.440 -20.160
Wk80 % change+ SE, postmenopausal females n=16, 10 3.017 8.297
Wk80 % change, postmenopausal females n=16, 10 -12.109 -9.170
Wk80% change - SE, postmenopausal females n=16, 10 -25.014 -23.807
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8682
Comments Overall population, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 1.467
Confidence Interval (2-Sided) 95%
-14.785 to 20.818
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9740
Comments Males, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 0.328
Confidence Interval (2-Sided) 95%
-18.308 to 23.214
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8378
Comments Females, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 2.986
Confidence Interval (2-Sided) 95%
-22.997 to 37.735
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7889
Comments Pre-menopausal females, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 8.190
Confidence Interval (2-Sided) 95%
-43.839 to 108.422
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8800
Comments Postmenopausal females, Week 80. Log transformed.
Method ANCOVA
Comments .Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 3.344
Confidence Interval (2-Sided) 95%
-34.853 to 63.935
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Hide Description Blood was taken for measurement of 25-hydroxy vitamin D. Percent change from baseline was based on log transformed data. Standard error, SE; Wk, Week; %, percent. This outcome measure was analyzed for a subset of participants in the bone study only. n is the number of evaluable participants, which is the number of participants with a value at baseline and at the specified visit for the parameter of interest.
Time Frame Baseline and Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with 25-hydroxy vitamin D measurements at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 45 38
Measure Type: Number
Unit of Measure: percent change
Wk80 % change + SE, overall n= 45, 38 -7.0053 -4.6305
Wk80 % change, overall n=45, 38 -13.9678 -12.9210
Wk 80 % change - SE, overall n= 45, 38 -20.4091 -20.4909
Wk80 % change + SE, males n=16, 21 8.9639 -4.2837
Wk80 % change, males n=16, 21 -4.4369 -14.1507
Wk80 % change - SE, males n=16, 21 -16.1896 -23.0005
Wk80 % change + SE, females n= 29, 17 -7.1080 4.7124
Wk80 % change, females n=29, 17 -16.4578 -9.0412
Wk 80 % change - SE, females n= 29, 17 -24.8664 -20.9882
Wk80 % change + SE, premenopausal females n=13, 7 -2.0833 0.3546
Wk80 % change, premenopausal females n= 13, 7 -15.3838 -16.2325
Wk80 % change - SE, premenopausal females n=13, 7 -26.8776 -30.0781
Wk80 % change+ SE, postmenopausal females n=16, 10 8.8368 17.3807
Wk80 % change, postmenopausal females n=16, 10 -7.1318 -2.7100
Wk80% change - SE, postmenopausal females n=16, 10 -20.7575 -19.3620
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9069
Comments Overall population, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 1.2168
Confidence Interval (2-Sided) 95%
-17.6057 to 24.3392
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5118
Comments Males, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value -10.1648
Confidence Interval (2-Sided) 95%
-35.6298 to 25.3742
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5816
Comments Females, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 8.8777
Confidence Interval (2-Sided) 95%
-20.2636 to 48.6692
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9587
Comments Pre-menopausal females, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value -1.0031
Confidence Interval (2-Sided) 95%
-35.9280 to 52.9590
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Metformin, Avandamet
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8337
Comments Postmenopausal females, Week 80. Log transformed.
Method ANCOVA
Comments Based on ANCOVA with terms for treatment, region, pre-screening HbA1c strata, sex, baseline.
Method of Estimation Estimation Parameter Percent difference from metformin
Estimated Value 4.7614
Confidence Interval (2-Sided) 95%
-34.4741 to 67.4901
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Hide Description Blood was taken for measurement of estradiol. Percent change from baseline was based on log transformed data. Standard error, SE; Wk, Week; %, percent. This outcome measure was analyzed for a subset of female participants in the bone study only. n is the number of evaluable participants, which is the number of female participants with a value at baseline and at the specified visit for the parameter of interest.
Time Frame Baseline and Weeks 20, 56, and 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Week 20 Evaluable for the Bone Sub-study Population. This is a subset of the bone sub-study with LOCF from Week 20. Only participants with estradiol measurements at Week 20 or later were included.
Arm/Group Title Metformin Avandamet
Hide Arm/Group Description:
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Overall Number of Participants Analyzed 30 22
Measure Type: Number
Unit of Measure: percent change
Wk80 % change + SE, females n= 30, 22 -8.695 0.097
Wk80 % change, females n=30, 22 -21.360 -15.441
Wk 80 % change - SE, females n= 30, 22 -32.268 -28.567
Wk56 % change + SE, females n= 27, 21 12.015 10.268
Wk56 % change, females n=27, 21 -0.815 -2.439
Wk 56 % change - SE, females n= 27, 21 -12.175 -13.682
Wk20 % change + SE, females n= 36, 25 7.863 14.875
Wk20 % change, females n=36, 25 -5.097 -0.646
Wk 20 % change - SE, females n= 36, 25 -16.500 -14.875
Wk80 % change + SE, premenopausal females n=13, 9 25.386 67.328
Wk80 % change, premenopausal females n= 13, 9 -17.314 7.667
Wk80 % change - SE, premenopausal females n=13, 9 -45.472 -30.722
Wk56 % change + SE, premenopausal females n=12, 8 35.708 19.557
Wk56 % change, premenopausal females n= 12, 8 1.677 -11.431
Wk56 % change - SE, premenopausal females n=12, 8 -23.820 -34.386
Wk20 % change + SE, premenopausal females n=15, 10 5.738 8.866
Wk20 % change, premenopausal females n=15, 10 -3.721 -3.005
Wk20 % change - SE, premenopausal females n=15, 10 -12.334 -13.581
Wk80 % change+ SE, postmenopausal females n=17, 13 -27.303 -25.501
Wk80 % change, postmenopausal females n=17, 13 -33.045 -31.754
Wk80% change - SE, postmenopausal females n=17, 13 -38.334 -37.482
Wk56 % change+ SE, postmenopausal females n=15, 13 -25.758 -18.475
Wk56 % change, postmenopausal females n=15, 13 -32.766 -25.372
Wk56% change - SE, postmenopausal females n=15, 13 -39.113 -31.686
Wk20 % change+ SE, postmenopausal females n=21, 15 3.432 16.140
Wk20 % change, postmenopausal females n=21, 15 -12.870 -5.061
Wk20% change - SE, postmenopausal females n=21, 15 -26.603 -22.391
Show Statistical Analysis 1