Trial Outcomes & Findings for A Type 2 Diabetes Study of the Longer-Term Glycemic Effect of AVANDAMET vs. Metformin (NCT NCT00386100)
NCT ID: NCT00386100
Last Updated: 2016-11-23
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
688 participants
Primary outcome timeframe
Baseline and Week 80
Results posted on
2016-11-23
Participant Flow
Participant milestones
| Measure |
Metformin
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
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 Study
STARTED
|
340
|
348
|
|
Overall Study
COMPLETED
|
186
|
217
|
|
Overall Study
NOT COMPLETED
|
154
|
131
|
Reasons for withdrawal
| Measure |
Metformin
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
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 Study
Did not receive study medication
|
6
|
4
|
|
Overall Study
Adverse Event
|
15
|
25
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Insufficient therapeutic effect
|
30
|
6
|
|
Overall Study
Lost to Follow-up
|
29
|
29
|
|
Overall Study
Non-compliance
|
18
|
19
|
|
Overall Study
Protocol Violation
|
5
|
3
|
|
Overall Study
Withdrawal by Subject
|
32
|
31
|
|
Overall Study
Bone mass density (BMD) loss >6%
|
4
|
4
|
|
Overall Study
BMD <2.5
|
1
|
0
|
|
Overall Study
Consecutive elevated Hba1C
|
1
|
0
|
|
Overall Study
Visit 11 DXA showed excessive bone loss
|
0
|
1
|
|
Overall Study
Laboratory findings
|
1
|
0
|
|
Overall Study
Participant's concern due to CPK levels
|
1
|
0
|
|
Overall Study
Participant moving out of state
|
2
|
0
|
|
Overall Study
Excessive bone loss vs. baseline value
|
0
|
1
|
|
Overall Study
Didn't meet entry criteria
|
1
|
1
|
|
Overall Study
Participant's PCP wanted to stop drug
|
1
|
0
|
|
Overall Study
Osteoporosis findings on Visit 2 DXA
|
0
|
1
|
|
Overall Study
Bad metabolic control & patient security
|
1
|
0
|
|
Overall Study
Bone loss by DXA bone scan
|
1
|
0
|
|
Overall Study
DBP 93 mmHg at randomization
|
1
|
0
|
|
Overall Study
7.6% bone loss
|
1
|
0
|
|
Overall Study
Osteoporosis
|
0
|
1
|
|
Overall Study
Positive pregnancy test
|
1
|
3
|
|
Overall Study
Out of country for 5 months
|
1
|
0
|
|
Overall Study
Hb1Ac >8%
|
0
|
1
|
|
Overall Study
Participant randomized in error
|
1
|
0
|
Baseline Characteristics
A Type 2 Diabetes Study of the Longer-Term Glycemic Effect of AVANDAMET vs. Metformin
Baseline characteristics by cohort
| Measure |
Metformin
n=334 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=344 Participants
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
n=678 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.7 years
STANDARD_DEVIATION 10.49 • n=5 Participants
|
51.5 years
STANDARD_DEVIATION 10.52 • n=7 Participants
|
51.1 years
STANDARD_DEVIATION 10.50 • n=5 Participants
|
|
Sex: Female, Male
Female
|
158 Participants
n=5 Participants
|
160 Participants
n=7 Participants
|
318 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
176 Participants
n=5 Participants
|
184 Participants
n=7 Participants
|
360 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African America/African
|
13 participants
n=5 Participants
|
17 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
3 participants
n=5 Participants
|
7 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - Central/South Asian
|
23 participants
n=5 Participants
|
22 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian
|
44 participants
n=5 Participants
|
51 participants
n=7 Participants
|
95 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - Japanese
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian
|
48 participants
n=5 Participants
|
48 participants
n=7 Participants
|
96 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European
|
185 participants
n=5 Participants
|
183 participants
n=7 Participants
|
368 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Specified
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Duration of Diabetes
|
2.570 years
STANDARD_DEVIATION 3.2671 • n=5 Participants
|
2.293 years
STANDARD_DEVIATION 3.0774 • n=7 Participants
|
2.429 years
STANDARD_DEVIATION 3.1729 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=294 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=301 Participants
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.
|
|---|---|---|
|
Change From Baseline in HbA1c at Week 80
Baseline
|
8.64 percent change
Standard Error 0.053
|
8.64 percent change
Standard Error 0.055
|
|
Change From Baseline in HbA1c at Week 80
Change from Baseline
|
-1.36 percent change
Standard Error 0.073
|
-1.85 percent change
Standard Error 0.070
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=258 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=265 Participants
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.
|
|---|---|---|
|
Mean Change From Baseline in HbA1c at Week 80
Baseline
|
8.59 percent change
Standard Deviation 0.898
|
8.66 percent change
Standard Deviation 0.954
|
|
Mean Change From Baseline in HbA1c at Week 80
Change from Baseline
|
-1.42 percent change
Standard Deviation 0.070
|
-1.91 percent change
Standard Deviation 0.069
|
SECONDARY outcome
Timeframe: Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=258 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=265 Participants
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.
|
|---|---|---|
|
Number of Participants Achieving HbA1c <=6.5% and <7% at Week 80
<=6.5%
|
97 participants
|
128 participants
|
|
Number of Participants Achieving HbA1c <=6.5% and <7% at Week 80
<7%
|
133 participants
|
184 participants
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
Blood was taken for serum FPG measurements. Change from baseline was calculated as the Week 80 value minus the baseline value.
Outcome measures
| Measure |
Metformin
n=319 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=332 Participants
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.
|
|---|---|---|
|
Change in Fasting Plasma Glucose (FPG) From Baseline at Week 80
Baseline
|
10.52 millimoles per Liter (mmol/l)
Standard Error 0.184
|
10.17 millimoles per Liter (mmol/l)
Standard Error 0.162
|
|
Change in Fasting Plasma Glucose (FPG) From Baseline at Week 80
Change from Baseline
|
-2.25 millimoles per Liter (mmol/l)
Standard Error 0.147
|
-3.41 millimoles per Liter (mmol/l)
Standard Error 0.139
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=258 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=265 Participants
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.
|
|---|---|---|
|
Change From Baseline in FPG at Week 80
Baseline
|
10.37 mmol/l
Standard Deviation 3.268
|
10.13 mmol/l
Standard Deviation 2.927
|
|
Change From Baseline in FPG at Week 80
Change from Baseline
|
-2.53 mmol/l
Standard Deviation 3.165
|
-3.39 mmol/l
Standard Deviation 2.908
|
SECONDARY outcome
Timeframe: Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=258 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=265 Participants
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.
|
|---|---|---|
|
Number of Participants Achieving FPG <=6 mmol/L (110 mg/dL) and <=7 mmol/L (126 mg/dL) at Week 80
FPG <=6.1 mmol/l
|
31 participants
|
83 participants
|
|
Number of Participants Achieving FPG <=6 mmol/L (110 mg/dL) and <=7 mmol/L (126 mg/dL) at Week 80
FPG <=7.0 mmol/l
|
55 participants
|
133 participants
|
SECONDARY outcome
Timeframe: Randomization to treatment failure (up to Week 80)Population: 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
Treatment failure was defined as an HbA1c level \>= 7% after Week 32 or withdrawal due to insufficient therapeutic effect (ITE) at any time.
Outcome measures
| Measure |
Metformin
n=319 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=332 Participants
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.
|
|---|---|---|
|
Number of Participants Achieving Treatment Failure
|
156 participants
|
114 participants
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=258 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=265 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change + SE, Total cholesterol, n=258, 265
|
-1.615 percent change
|
4.218 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change, Total cholesterol, n=258, 265
|
-2.89 percent change
|
2.91 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change - SE, Total cholesterol, n=258, 265
|
-4.140 percent change
|
1.614 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change + SE, LDL cholesterol, n=248, 252
|
-4.933 percent change
|
3.304 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change, LDL cholesterol, n=248, 252
|
-7.11 percent change
|
0.98 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change - SE, LDL cholesterol, n=248, 252
|
-9.228 percent change
|
-1.286 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change + SE, HDL cholesterol, n=258, 265
|
6.761 percent change
|
9.483 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change, HDL cholesterol, n=258, 265
|
5.60 percent change
|
8.324 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change - SE, HDL cholesterol, n=258, 265
|
4.453 percent change
|
7.179 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change + SE, triglycerides, n=258, 265
|
-2.696 percent change
|
-2.042 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change, triglycerides, n=258, 265
|
-5.330 percent change
|
-4.627 percent change
|
|
Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80
% change - SE, triglycerides, n=258, 265
|
-7.893 percent change
|
-7.143 percent change
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=91 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=96 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Adiponectin at Week 80 (United States [US] and Mexico Subset of Participants )
Percent change from baseline - SE
|
7.61 percent change
|
118.10 percent change
|
|
Percent Change From Baseline in Adiponectin at Week 80 (United States [US] and Mexico Subset of Participants )
Percent change from baseline + SE
|
18.58 percent change
|
139.28 percent change
|
|
Percent Change From Baseline in Adiponectin at Week 80 (United States [US] and Mexico Subset of Participants )
Percent change from baseline
|
12.96 percent change
|
128.44 percent change
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=92 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=95 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in C-reactive Protein (CRP) at Week 80 (US and Mexico Subset of Participants)
Percent change from baseline + SE
|
-6.49 percent change
|
14.28 percent change
|
|
Percent Change From Baseline in C-reactive Protein (CRP) at Week 80 (US and Mexico Subset of Participants)
Percent change from baseline
|
-10.63 percent change
|
-17.96 percent change
|
|
Percent Change From Baseline in C-reactive Protein (CRP) at Week 80 (US and Mexico Subset of Participants)
Percent change from baseline - SE
|
-14.59 percent change
|
-21.49 percent change
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=92 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=95 Participants
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.
|
|---|---|---|
|
Percent Change in Free Fatty Acids (FFA) From Baseline at Week 80 (US and Mexico Subset of Participants).
Percent change from baseline + SE
|
14.353 percent change
|
1.267 percent change
|
|
Percent Change in Free Fatty Acids (FFA) From Baseline at Week 80 (US and Mexico Subset of Participants).
Percent change from baseline
|
9.40 percent change
|
-2.97 percent change
|
|
Percent Change in Free Fatty Acids (FFA) From Baseline at Week 80 (US and Mexico Subset of Participants).
Percent change from baseline - SE
|
4.657 percent change
|
-7.028 percent change
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=92 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=97 Participants
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.
|
|---|---|---|
|
Change in Fasting Insulin From Baseline at Week 80 (US and Mexico Subset of Participants)
|
-1.5 picomoles per Liter (pmol/l)
Standard Error 9.18
|
-35.2 picomoles per Liter (pmol/l)
Standard Error 8.79
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=92 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=95 Participants
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.
|
|---|---|---|
|
Change in C-peptide From Baseline at Week 80 (US and Mexico Subset of Participants)
|
-0.244 mmol/l
Standard Error 0.0518
|
-0.473 mmol/l
Standard Error 0.0502
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=91 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=96 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)
Percent change HOMA-B + SE
|
88.25 percent change
|
92.32 percent change
|
|
Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)
Percent change HOMA-B
|
78.85 percent change
|
83.14 percent change
|
|
Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)
Percent change HOMA-B - SE
|
69.92 percent change
|
74.39 percent change
|
|
Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)
Percent change HOMA-S + SE
|
25.13 percent change
|
63.67 percent change
|
|
Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)
Percent change HOMA-S
|
18.65 percent change
|
55.58 percent change
|
|
Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)
Percent change HOMA-S - SE
|
12.49 percent change
|
47.91 percent change
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=82 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=89 Participants
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.
|
|---|---|---|
|
Slope of Delta-cell Function as Estimated by the Ratio deltaI/deltaG
|
-86.23 ratio
Standard Error 59.706
|
-5.38 ratio
Standard Error 55.229
|
SECONDARY outcome
Timeframe: Baseline to Week 80 or withdrawalPopulation: Safety population. This population consisted of all participants who were randomized and received at least one dose of the study medication.
Outcome measures
| Measure |
Metformin
n=334 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=344 Participants
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.
|
|---|---|---|
|
Number of Participants at Final Dose Level
Dose level 1 AVM 4 mg/500 mg, MET 500 mg
|
17 participants
|
19 participants
|
|
Number of Participants at Final Dose Level
Dose level 2 AVM 4 mg/1000 mg, MET 1000 mg
|
16 participants
|
18 participants
|
|
Number of Participants at Final Dose Level
Dose level 3 AVM 6 mg/1500 mg, MET 1500 mg
|
27 participants
|
34 participants
|
|
Number of Participants at Final Dose Level
Dose level 4 AVM 8 mg/2000 mg, MET 2000 mg
|
236 participants
|
242 participants
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=87 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=87 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 80, n=87, 87
|
-2.1 percent change
Standard Error 0.54
|
0.1 percent change
Standard Error 0.54
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 56, n=87, 87
|
-1.4 percent change
Standard Error 0.45
|
0.3 percent change
Standard Error 0.44
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 20, n=87, 87
|
-0.5 percent change
Standard Error 0.41
|
0.5 percent change
Standard Error 0.40
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 80, n=38, 43
|
-0.7 percent change
Standard Error 0.81
|
1.0 percent change
Standard Error 0.90
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 56, n=38, 43
|
-0.2 percent change
Standard Error 0.61
|
0.7 percent change
Standard Error 0.68
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 20, n=38, 43
|
-0.1 percent change
Standard Error 0.63
|
-0.2 percent change
Standard Error 0.71
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 80, n=49, 44
|
-2.7 percent change
Standard Error 0.77
|
0.2 percent change
Standard Error 0.75
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 56, n=49, 44
|
-2.0 percent change
Standard Error 0.70
|
0.3 percent change
Standard Error 0.68
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 20, n=49, 44
|
-0.9 percent change
Standard Error 0.52
|
1.2 percent change
Standard Error 0.51
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 80, n=21, 14
|
-2.4 percent change
Standard Error 1.01
|
-0.7 percent change
Standard Error 1.03
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 56, n=21, 14
|
-0.8 percent change
Standard Error 0.88
|
0.2 percent change
Standard Error 0.90
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 20, n=21, 14
|
0.2 percent change
Standard Error 0.75
|
0.5 percent change
Standard Error 0.77
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 80, n=28, 30
|
-3.3 percent change
Standard Error 1.22
|
0 percent change
Standard Error 1.16
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 56, n=28, 30
|
-2.7 percent change
Standard Error 1.09
|
-0.1 percent change
Standard Error 1.04
|
|
Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 20, n=28, 30
|
-1.4 percent change
Standard Error 0.73
|
-1.1 percent change
Standard Error 0.69
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=87 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=87 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 56, n=28, 30
|
-1.1 percent change
Standard Error 0.81
|
-1.5 percent change
Standard Error 0.85
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 80, n=87, 87
|
0.0 percent change
Standard Error 0.35
|
-1.5 percent change
Standard Error 0.35
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 56, n=87, 87
|
-0.2 percent change
Standard Error 0.31
|
-1.2 percent change
Standard Error 0.32
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 20, n=87, 87
|
0.2 percent change
Standard Error 0.24
|
-0.4 percent change
Standard Error 0.24
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 80, n=38, 43
|
0.3 percent change
Standard Error 0.46
|
-1.0 percent change
Standard Error 0.41
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 56, n=38, 43
|
0.2 percent change
Standard Error 0.41
|
-0.8 percent change
Standard Error 0.37
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 20, n=38, 43
|
0.5 percent change
Standard Error 0.35
|
-0.3 percent change
Standard Error 0.31
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 80, n=49, 44
|
0.0 percent change
Standard Error 0.60
|
-1.8 percent change
Standard Error 0.61
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 56, n=49, 44
|
-0.2 percent change
Standard Error 0.52
|
-1.4 percent change
Standard Error 0.54
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 20, n=49, 44
|
-0.3 percent change
Standard Error 0.37
|
-0.6 percent change
Standard Error 0.38
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 80, n=21, 14
|
1.3 percent change
Standard Error 0.71
|
-0.9 percent change
Standard Error 0.69
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 56, n=21, 14
|
0.8 percent change
Standard Error 0.69
|
-1.6 percent change
Standard Error 0.67
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 20, n=21, 14
|
0.3 percent change
Standard Error 0.48
|
0.0 percent change
Standard Error 0.47
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 80, n=28, 30
|
-0.9 percent change
Standard Error 0.97
|
-2.3 percent change
Standard Error 1.02
|
|
Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 20, n=28, 30
|
-0.4 percent change
Standard Error 0.57
|
-0.6 percent change
Standard Error 0.60
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=87 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=87 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 56, n=49, 44
|
-0.3 percent change
Standard Error 0.80
|
-2.1 percent change
Standard Error 0.82
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 20, n=49, 44
|
-0.2 percent change
Standard Error 0.52
|
-0.8 percent change
Standard Error 0.53
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 80, n=87, 87
|
-0.1 percent change
Standard Error 0.54
|
-2.1 percent change
Standard Error 0.55
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 56, n=87, 87
|
-0.2 percent change
Standard Error 0.49
|
-1.7 percent change
Standard Error 0.49
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 20, n=87, 87
|
0.1 percent change
Standard Error 0.35
|
-0.6 percent change
Standard Error 0.34
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 80, n=38, 43
|
1.1 percent change
Standard Error 0.69
|
-0.4 percent change
Standard Error 0.61
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 56, n=38, 43
|
0.9 percent change
Standard Error 0.67
|
-0.5 percent change
Standard Error 0.60
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 20, n=38, 43
|
0.7 percent change
Standard Error 0.55
|
-0.2 percent change
Standard Error 0.48
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 80, n=49, 44
|
-0.2 percent change
Standard Error 0.93
|
-2.6 percent change
Standard Error 0.96
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 80, n=21, 14
|
1.7 percent change
Standard Error 1.18
|
-1.4 percent change
Standard Error 1.12
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 56, n=21, 14
|
0.3 percent change
Standard Error 0.94
|
-2.6 percent change
Standard Error 0.89
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 20, n=21, 14
|
0.0 percent change
Standard Error 0.71
|
0.0 percent change
Standard Error 0.67
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 80, n=28, 30
|
-1.1 percent change
Standard Error 1.45
|
-3.6 percent change
Standard Error 1.53
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 56, n=28, 30
|
-1.1 percent change
Standard Error 1.25
|
-2.2 percent change
Standard Error 1.31
|
|
Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 20, n=28, 30
|
-0.3 percent change
Standard Error 0.76
|
-1.0 percent change
Standard Error 0.80
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=87 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=87 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 20, n=28, 30
|
-1.1 percent change
Standard Error 0.71
|
-0.4 percent change
Standard Error 0.74
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 80, n=87, 87
|
-0.7 percent change
Standard Error 0.39
|
-1.4 percent change
Standard Error 0.39
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 56, n=87, 87
|
-0.7 percent change
Standard Error 0.39
|
-0.8 percent change
Standard Error 0.39
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 20, n=87, 87
|
-0.1 percent change
Standard Error 0.36
|
-0.2 percent change
Standard Error 0.36
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 80, n=38, 43
|
-1.4 percent change
Standard Error 0.66
|
-2.2 percent change
Standard Error 0.59
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 56, n=38, 43
|
-0.7 percent change
Standard Error 0.64
|
-1.3 percent change
Standard Error 0.57
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 20, n=38, 43
|
-0.4 percent change
Standard Error 0.60
|
-0.7 percent change
Standard Error 0.53
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 80, n=49, 44
|
-0.3 percent change
Standard Error 0.56
|
-1.2 percent change
Standard Error 0.57
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 56, n=49, 44
|
-0.6 percent change
Standard Error 0.55
|
-0.5 percent change
Standard Error 0.56
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 20, n=49, 44
|
-0.4 percent change
Standard Error 0.49
|
-0.2 percent change
Standard Error 0.50
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 80, n=21, 14
|
0.9 percent change
Standard Error 0.73
|
-0.3 percent change
Standard Error 0.68
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 56, n=21, 14
|
-0.1 percent change
Standard Error 0.96
|
-0.4 percent change
Standard Error 0.89
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 20, n=21, 14
|
0.9 percent change
Standard Error 0.83
|
-0.3 percent change
Standard Error 0.77
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 80, n=28, 30
|
-1.3 percent change
Standard Error 0.87
|
-2.1 percent change
Standard Error 0.91
|
|
Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 56, n=28, 30
|
-1.2 percent change
Standard Error 0.81
|
-0.7 percent change
Standard Error 0.85
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=87 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=87 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 20, n=87, 87
|
1.2 percent change
Standard Error 0.58
|
0.9 percent change
Standard Error 0.61
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 80, n=38, 43
|
0.4 percent change
Standard Error 0.84
|
-0.6 percent change
Standard Error 0.82
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 20, n=38, 43
|
1.5 percent change
Standard Error 0.75
|
0.2 percent change
Standard Error 0.73
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 80, n=21, 14
|
1.1 percent change
Standard Error 1.51
|
-0.3 percent change
Standard Error 1.44
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 80, n=87, 87
|
0.3 percent change
Standard Error 0.63
|
-0.1 percent change
Standard Error 0.66
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 56, n=87, 87
|
0.5 percent change
Standard Error 0.55
|
0.5 percent change
Standard Error 0.58
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 56, n=38, 43
|
0.7 percent change
Standard Error 0.73
|
0.4 percent change
Standard Error 0.71
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 80, n=49, 44
|
0.1 percent change
Standard Error 1.00
|
0.1 percent change
Standard Error 1.07
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 56, n=49, 44
|
0.6 percent change
Standard Error 0.87
|
0.7 percent change
Standard Error 0.93
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 20, n=49, 44
|
0.6 percent change
Standard Error 0.94
|
1.1 percent change
Standard Error 0.99
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 56, n=21, 14
|
2.2 percent change
Standard Error 1.37
|
-0.6 percent change
Standard Error 1.30
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 20, n=21, 14
|
2.6 percent change
Standard Error 1.51
|
0.7 percent change
Standard Error 1.40
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 80, n=28, 30
|
-0.5 percent change
Standard Error 1.61
|
-0.2 percent change
Standard Error 1.76
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 56, n=28, 30
|
-0.3 percent change
Standard Error 1.34
|
0.8 percent change
Standard Error 1.46
|
|
Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 20, n=28, 30
|
0.5 percent change
Standard Error 1.36
|
1.3 percent change
Standard Error 1.49
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=87 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=87 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 80, n=87, 87
|
1.1 percent change
Standard Error 0.64
|
1.1 percent change
Standard Error 0.64
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 56, n=87, 87
|
1.3 percent change
Standard Error 0.63
|
-0.1 percent change
Standard Error 0.63
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Overall population, Week 20, n=87, 87
|
0.0 percent change
Standard Error 0.37
|
0.5 percent change
Standard Error 0.37
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 80, n=38, 43
|
0.3 percent change
Standard Error 0.43
|
0.5 percent change
Standard Error 0.38
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 56, n=38, 43
|
0.5 percent change
Standard Error 0.41
|
0.5 percent change
Standard Error 0.37
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Male population, Week 20, n=38, 43
|
0.2 percent change
Standard Error 0.43
|
0.5 percent change
Standard Error 0.38
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 80, n=49, 44
|
2.0 percent change
Standard Error 1.00
|
1.0 percent change
Standard Error 1.01
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 56, n=49, 44
|
1.9 percent change
Standard Error 1.03
|
1.2 percent change
Standard Error 1.04
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Female population, Week 20, n=49, 44
|
-0.2 percent change
Standard Error 0.56
|
0.5 percent change
Standard Error 0.57
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 80, n=21, 14
|
5.3 percent change
Standard Error 2.26
|
-0.2 percent change
Standard Error 2.73
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 56, n=21, 14
|
5.2 percent change
Standard Error 2.42
|
-1.0 percent change
Standard Error 2.94
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Premenopausal population, Week 20, n=21, 14
|
-0.2 percent change
Standard Error 1.38
|
0.3 percent change
Standard Error 1.66
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 80, n=28, 30
|
0.2 percent change
Standard Error 0.56
|
-0.4 percent change
Standard Error 0.67
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 56, n=28, 30
|
-0.2 percent change
Standard Error 0.49
|
-0.6 percent change
Standard Error 0.58
|
|
Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)
Postmenopausal population, Week 20, n=28, 30
|
-0.2 percent change
Standard Error 0.45
|
0.1 percent change
Standard Error 0.54
|
SECONDARY outcome
Timeframe: Baseline and Weeks 12, 32, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=79 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=79 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change - SE, males n 33,39
|
-2.019 percent change
|
-1.919 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change + SE, males n=37, 40
|
1.410 percent change
|
0.543 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change - SE, females n= 45, 38
|
-0.557 percent change
|
-1.930 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change, females n=44, 38
|
0.055 percent change
|
-1.081 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change - SE, females n= 44, 38
|
-0.600 percent change
|
-1.733 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change + SE, overall n= 79, 79
|
0.929 percent change
|
1.104 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change, overall n=79, 79
|
0.424 percent change
|
0.592 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change - SE, overall n= 79, 79
|
-0.079 percent change
|
0.083 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change + SE, overall n= 79, 79
|
1.098 percent change
|
1.313 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change, overall n= 79, 79
|
0.527 percent change
|
0.735 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change - SE, overall n 79, 79
|
-0.040 percent change
|
0.160 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change + SE, overall n=78, 77
|
0.136 percent change
|
-0.735 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change, overall n= 78, 77
|
-0.316 percent change
|
-1.204 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change - SE, overall n 78, 79
|
-0.766 percent change
|
-1.607 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change + SE, overall n=81, 78
|
0.568 percent change
|
-0.315 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change, overall n= 81, 78
|
0.123 percent change
|
-0.767 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change - SE, overall n 81, 78
|
-0.320 percent change
|
-1.216 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change + SE, males n=34, 39
|
0.8777 percent change
|
1.551 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change, males n= 34, 39
|
0.071 percent change
|
0.817 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change - SE, males n 34, 39
|
-0.728 percent change
|
0.877 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change + SE, males n=34, 39
|
1.304 percent change
|
1.092 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change, males n= 34, 39
|
0.646 percent change
|
0.498 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change - SE, males n 34, 39
|
-0.009 percent change
|
-0.094 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change + SE, males n=33, 39
|
-0.538 percent change
|
-0.585 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change, males n= 33, 39
|
-1.281 percent change
|
-1.254 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change, males n= 37, 40
|
0.656 percent change
|
-0.147 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change - SE, males n 37, 40
|
-0.091 percent change
|
-0.833 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change + SE, females n= 45, 40
|
1.508 percent change
|
1.049 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change, females n=45, 40
|
0.735 percent change
|
0.279 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change - SE, females n= 45, 40
|
-0.033 percent change
|
-0.484 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change + SE, females n= 45, 40
|
1.692 percent change
|
1.884 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change, females n=45, 40
|
0.720 percent change
|
0.911 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change - SE, females n= 45, 40
|
-0.242 percent change
|
-0.053 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change + SE, females n= 45, 38
|
0.637 percent change
|
-0.653 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change, females n=45, 38
|
0.038 percent change
|
-1.293 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change + SE, females n= 44, 38
|
0.715 percent change
|
-0.425 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change + SE, premenopausal females n=19, 14
|
1.429 percent change
|
0.704 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change, premenopausal females n= 19, 14
|
0.531 percent change
|
-0.111 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change - SE, premenopausal females n 19, 14
|
-0.359 percent change
|
-0.918 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change + SE, premenopausal females n=19, 14
|
2.091 percent change
|
2.334 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change, premenopausal females n= 19, 14
|
0.960 percent change
|
1.298 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change - SE, premenopausal females n 19, 14
|
-0.159 percent change
|
0.273 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change + SE, premenopausal females n=19, 13
|
1.074 percent change
|
-0.650 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change, premenopausal females n= 19, 13
|
0.070 percent change
|
-1.679 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change - SE, premenopausal females n 19, 13
|
-0.923 percent change
|
-2.698 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change + SE, premenopausal females n=19, 13
|
0.420 percent change
|
-0.218 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change, premenopausal females n= 19, 13
|
-0.657 percent change
|
-1.280 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change - SE, premenopausal females n 19, 13
|
-1.722 percent change
|
-2.330 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change+ SE, postmenopausal females n=26, 26
|
2.019 percent change
|
1.915 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80 % change, postmenopausal females n=26, 26
|
0.760 percent change
|
0.604 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk80% change - SE, postmenopausal females n=26, 26
|
-0.484 percent change
|
-0.690 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change+ SE, postmenopausal females n=26, 26
|
2.181 percent change
|
2.691 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56 % change, postmenopausal females n=26, 26
|
0.560 percent change
|
0.993 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk56% change - SE, postmenopausal females n=26, 26
|
-1.035 percent change
|
-0.677 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change+ SE, postmenopausal females n=26, 25
|
0.844 percent change
|
-0.535 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32 % change, postmenopausal females n=26, 25
|
0.056 percent change
|
-1.360 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk32% change - SE, postmenopausal females n=26, 25
|
-0.726 percent change
|
-2.178 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change+ SE, postmenopausal females n=25, 25
|
0.844 percent change
|
-1.163 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12 % change, postmenopausal females n=25, 25
|
-0.042 percent change
|
-2.074 percent change
|
|
Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80
Wk12% change - SE, postmenopausal females n=25, 25
|
-0.921 percent change
|
-2.976 percent change
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=45 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=38 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change + SE, overall n= 45, 38
|
-1.296 percent change
|
0.843 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change, overall n=45, 38
|
-7.634 percent change
|
-6.279 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change - SE, overall n= 45, 38
|
-13.565 percent change
|
-12.898 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change + SE, males n=16, 21
|
-1.160 percent change
|
-2.619 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change, males n= 16, 21
|
-9.238 percent change
|
-8.941 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change - SE, males n=16, 21
|
-16.655 percent change
|
-14.852 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change + SE, females n= 30, 22
|
4.662 percent change
|
11.166 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change, females n=30, 22
|
-4.608 percent change
|
-1.759 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk 80 % change - SE, females n= 30, 22
|
-13.056 percent change
|
-13.182 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change + SE, premenopausal females n=13, 7
|
14.295 percent change
|
24.396 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change, premenopausal females n= 13, 7
|
-7.686 percent change
|
-0.126 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change - SE, premenopausal females n=13, 7
|
-25.440 percent change
|
-20.160 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change+ SE, postmenopausal females n=16, 10
|
3.017 percent change
|
8.297 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80 % change, postmenopausal females n=16, 10
|
-12.109 percent change
|
-9.170 percent change
|
|
Percent Change From Baseline in Intact Parathyroid Hormone at Week 80
Wk80% change - SE, postmenopausal females n=16, 10
|
-25.014 percent change
|
-23.807 percent change
|
SECONDARY outcome
Timeframe: Baseline and Week 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=45 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=38 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change, premenopausal females n= 13, 7
|
-15.3838 percent change
|
-16.2325 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change + SE, overall n= 45, 38
|
-7.0053 percent change
|
-4.6305 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change, overall n=45, 38
|
-13.9678 percent change
|
-12.9210 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk 80 % change - SE, overall n= 45, 38
|
-20.4091 percent change
|
-20.4909 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change + SE, males n=16, 21
|
8.9639 percent change
|
-4.2837 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change, males n=16, 21
|
-4.4369 percent change
|
-14.1507 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change - SE, males n=16, 21
|
-16.1896 percent change
|
-23.0005 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change + SE, females n= 29, 17
|
-7.1080 percent change
|
4.7124 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change, females n=29, 17
|
-16.4578 percent change
|
-9.0412 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk 80 % change - SE, females n= 29, 17
|
-24.8664 percent change
|
-20.9882 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change + SE, premenopausal females n=13, 7
|
-2.0833 percent change
|
0.3546 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change - SE, premenopausal females n=13, 7
|
-26.8776 percent change
|
-30.0781 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change+ SE, postmenopausal females n=16, 10
|
8.8368 percent change
|
17.3807 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80 % change, postmenopausal females n=16, 10
|
-7.1318 percent change
|
-2.7100 percent change
|
|
Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80
Wk80% change - SE, postmenopausal females n=16, 10
|
-20.7575 percent change
|
-19.3620 percent change
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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.
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.
Outcome measures
| Measure |
Metformin
n=30 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=22 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56 % change, females n=27, 21
|
-0.815 percent change
|
-2.439 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk 56 % change - SE, females n= 27, 21
|
-12.175 percent change
|
-13.682 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20 % change + SE, females n= 36, 25
|
7.863 percent change
|
14.875 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80 % change + SE, females n= 30, 22
|
-8.695 percent change
|
0.097 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80 % change, females n=30, 22
|
-21.360 percent change
|
-15.441 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk 80 % change - SE, females n= 30, 22
|
-32.268 percent change
|
-28.567 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56 % change + SE, females n= 27, 21
|
12.015 percent change
|
10.268 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20 % change, females n=36, 25
|
-5.097 percent change
|
-0.646 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk 20 % change - SE, females n= 36, 25
|
-16.500 percent change
|
-14.875 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80 % change + SE, premenopausal females n=13, 9
|
25.386 percent change
|
67.328 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80 % change, premenopausal females n= 13, 9
|
-17.314 percent change
|
7.667 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80 % change - SE, premenopausal females n=13, 9
|
-45.472 percent change
|
-30.722 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56 % change + SE, premenopausal females n=12, 8
|
35.708 percent change
|
19.557 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56 % change, premenopausal females n= 12, 8
|
1.677 percent change
|
-11.431 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56 % change - SE, premenopausal females n=12, 8
|
-23.820 percent change
|
-34.386 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20 % change + SE, premenopausal females n=15, 10
|
5.738 percent change
|
8.866 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20 % change, premenopausal females n=15, 10
|
-3.721 percent change
|
-3.005 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20 % change - SE, premenopausal females n=15, 10
|
-12.334 percent change
|
-13.581 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80 % change+ SE, postmenopausal females n=17, 13
|
-27.303 percent change
|
-25.501 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80 % change, postmenopausal females n=17, 13
|
-33.045 percent change
|
-31.754 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk80% change - SE, postmenopausal females n=17, 13
|
-38.334 percent change
|
-37.482 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56 % change+ SE, postmenopausal females n=15, 13
|
-25.758 percent change
|
-18.475 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56 % change, postmenopausal females n=15, 13
|
-32.766 percent change
|
-25.372 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk56% change - SE, postmenopausal females n=15, 13
|
-39.113 percent change
|
-31.686 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20 % change+ SE, postmenopausal females n=21, 15
|
3.432 percent change
|
16.140 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20 % change, postmenopausal females n=21, 15
|
-12.870 percent change
|
-5.061 percent change
|
|
Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80
Wk20% change - SE, postmenopausal females n=21, 15
|
-26.603 percent change
|
-22.391 percent change
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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 CTX measurements at Week 20 or later were included.
Blood was taken for measurement of CTX. 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.
Outcome measures
| Measure |
Metformin
n=69 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=62 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change+ SE, postmenopausal females n=22, 21
|
10.3 percent change
|
5.1 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change + SE, overall n=69, 62
|
-12.7 percent change
|
-7.5 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change, overall n=69, 62
|
-18.7 percent change
|
-14.0 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change - SE, overall n=79, 62
|
-24.2 percent change
|
-20.1 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change + SE, overall n=68, 62
|
-5.3 percent change
|
3.7 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change, overall n=68, 62
|
-11.4 percent change
|
-3.2 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change - SE, overall n=68, 62
|
-17.1 percent change
|
-9.6 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change + SE, overall n=61, 56
|
-0.8 percent change
|
-0.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change, overall n=61, 56
|
-5.5 percent change
|
-5.9 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change - SE, overall n=61, 56
|
-9.9 percent change
|
-10.7 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change + SE, males n=28, 32
|
-11.0 percent change
|
-1.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change, males n=28, 32
|
-20.7 percent change
|
-10.9 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change - SE, males n=28, 32
|
-29.2 percent change
|
-19.1 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change + SE, males n=28, 32
|
-11.5 percent change
|
6.5 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change, males n=28, 32
|
-20.0 percent change
|
-2.2 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change - SE, males n=28, 32
|
-27.7 percent change
|
-10.2 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change + SE, males n=23, 29
|
4.8 percent change
|
13.2 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change, males n=23, 29
|
-3.1 percent change
|
5.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change - SE, males n=23, 29
|
-10.3 percent change
|
-1.1 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change + SE, females n=41, 30
|
-12.9 percent change
|
-8.2 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change, females n=41, 30
|
-20.1 percent change
|
-16.9 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change - SE, females n=41, 30
|
-26.6 percent change
|
-24.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change + SE, females n=40, 30
|
-8.5 percent change
|
1.2 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change, females n=40, 30
|
-15.8 percent change
|
-8.0 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change - SE, females n=40, 30
|
-22.5 percent change
|
-16.4 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change + SE, females n=38, 27
|
-2.5 percent change
|
-8.3 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change, females n=38, 27
|
-8.9 percent change
|
-15.3 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change - SE, females n=38, 27
|
-15.0 percent change
|
-21.7 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change + SE, premenopausal females n=18, 9
|
-18.6 percent change
|
10.9 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change, premenopausal females n=18, 9
|
-27.8 percent change
|
-4.7 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change - SE, premenopausal females n=18, 9
|
-36.0 percent change
|
-18.1 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change + SE, premenopausal females n=18, 9
|
-25.5 percent change
|
12.6 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change, premenopausal females n=18, 9
|
-31.8 percent change
|
0.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change - SE, premenopausal females n=18, 9
|
-37.5 percent change
|
-9.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change + SE, premenopausal females n=16, 9
|
-4.2 percent change
|
-7.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change, premenopausal females n=16, 9
|
-14.0 percent change
|
-18.9 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change - SE, premenopausal females n=16, 9
|
-22.8 percent change
|
-28.8 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change+ SE, postmenopausal females n=23, 21
|
-11.5 percent change
|
-14.3 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80 % change, postmenopausal females n=23, 21
|
-21.0 percent change
|
-24.4 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk80% change - SE, postmenopausal females n=23, 21
|
-29.5 percent change
|
-33.4 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56 % change, postmenopausal females n=22, 21
|
-2.1 percent change
|
-7.4 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk56% change - SE, postmenopausal females n=22, 21
|
-13.0 percent change
|
-18.4 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change+ SE, postmenopausal females n=22, 18
|
4.1 percent change
|
-3.2 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20 % change, postmenopausal females n=22, 18
|
-5.8 percent change
|
-13.6 percent change
|
|
Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80
Wk20% change - SE, postmenopausal females n=22, 18
|
-14.7 percent change
|
-22.8 percent change
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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 P1NP measurements at Week 20 or later were included.
Blood was taken for measurement of P1NP. 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.
Outcome measures
| Measure |
Metformin
n=72 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=64 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change + SE, overall n= 72, 64
|
-18.4 percent change
|
-20.7 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change, overall n=72, 64
|
-22.0 percent change
|
-24.3 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change - SE, overall n=72, 64
|
-25.5 percent change
|
-27.8 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change + SE, overall n=72, 64
|
-23.5 percent change
|
-26.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change, overall n=72, 64
|
-26.9 percent change
|
-30.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change - SE, overall n=72, 64
|
-30.2 percent change
|
-33.3 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change + SE, overall n=66, 59
|
-24.0 percent change
|
-31.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change, overall n=66, 59
|
-27.0 percent change
|
-34.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change - SE, overall n=66, 59
|
-30.0 percent change
|
-37.5 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change + SE, males n=30, 32
|
-18.5 percent change
|
-18.2 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change, males n=30, 32
|
-24.1 percent change
|
-23.4 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change - SE, males n=30, 32
|
-29.4 percent change
|
-28.2 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change + SE, males n=30, 32
|
-22.7 percent change
|
-23.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change, males n=30, 32
|
-27.7 percent change
|
-27.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change - SE, males n=30, 32
|
-32.4 percent change
|
-31.9 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change + SE, males n=26, 29
|
-20.2 percent change
|
-24.7 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change, males n=26, 29
|
-25.4 percent change
|
-29.5 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change - SE, males n=26, 29
|
-30.3 percent change
|
-33.9 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change + SE, females n=42, 32
|
-19.3 percent change
|
-19.2 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change, females n=42, 32
|
-23.8 percent change
|
-24.4 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change - SE, females n=42, 32
|
-28.2 percent change
|
-29.3 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change + SE, females n=42, 32
|
-28.6 percent change
|
-27.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change, females n=42, 32
|
-32.8 percent change
|
-32.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change - SE, females n=42, 32
|
-36.9 percent change
|
-36.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change + SE, females n=40, 30
|
-25.2 percent change
|
-31.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change, females n=40, 30
|
-30.0 percent change
|
-36.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change - SE, females n=40, 30
|
-34.5 percent change
|
-41.2 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change + SE, premenopausal females n=19, 10
|
-16.9 percent change
|
-11.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change, premenopausal females n=19, 10
|
-23.6 percent change
|
-20.1 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change - SE, premenopausal females n=19, 10
|
-29.7 percent change
|
-28.3 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change + SE, premenopausal females n=19, 10
|
-25.3 percent change
|
-23.4 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change, premenopausal females n=19, 10
|
-31.0 percent change
|
-30.9 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change - SE, premenopausal females n=19, 10
|
-36.2 percent change
|
-37.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change + SE, premenopausal females n=17, 10
|
-24.6 percent change
|
-29.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change, premenopausal females n=17, 10
|
-31.4 percent change
|
-36.5 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change - SE, premenopausal females n=17, 10
|
-37.7 percent change
|
-43.1 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change+ SE, postmenopausal females n=23, 22
|
-22.5 percent change
|
-27.6 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80 % change, postmenopausal females n=23, 22
|
-28.4 percent change
|
-33.8 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk80% change - SE, postmenopausal females n=23, 22
|
-33.8 percent change
|
-39.4 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change+ SE, postmenopausal females n=23, 22
|
-32.1 percent change
|
-35.2 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56 % change, postmenopausal females n=23, 22
|
-37.9 percent change
|
-41.4 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk56% change - SE, postmenopausal females n=22, 22
|
-43.2 percent change
|
-47.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change+ SE, postmenopausal females n=23, 20
|
-25.2 percent change
|
-34.0 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20 % change, postmenopausal females n=23, 20
|
-31.9 percent change
|
-40.9 percent change
|
|
Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Wk20% change - SE, postmenopausal females n=23, 20
|
-38.0 percent change
|
-47.1 percent change
|
SECONDARY outcome
Timeframe: Baseline and Weeks 20, 56, and 80Population: 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 BSAP measurements at Week 20 or later were included.
Blood was taken for measurement of BSAP. 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.
Outcome measures
| Measure |
Metformin
n=72 Participants
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=64 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change, males n=30, 32
|
-17.05 percent change
|
-25.87 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change, females n=40, 30
|
-30.23 percent change
|
-35.23 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change, premenopausal females n=19, 10
|
-16.84 percent change
|
-32.47 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change - SE, premenopausal females n=19, 10
|
-21.02 percent change
|
-36.89 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change + SE, premenopausal females n=17, 10
|
-24.73 percent change
|
-32.69 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change, premenopausal females n=17, 10
|
-29.57 percent change
|
-37.68 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80% change - SE, postmenopausal females n=23, 22
|
-39.29 percent change
|
-37.54 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change + SE, overall n=72, 64
|
-21.19 percent change
|
-23.30 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change, overall n=72, 64
|
-24.23 percent change
|
-26.37 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change - SE, overall n=72, 64
|
-27.15 percent change
|
-29.31 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change + SE, overall n=72, 64
|
-18.29 percent change
|
-24.39 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change, overall n=72, 64
|
-21.52 percent change
|
-27.48 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change - SE, overall n=72, 64
|
-24.61 percent change
|
-30.45 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change + SE, overall n=66, 59
|
-24.16 percent change
|
-31.02 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change, overall n=66, 59
|
-26.46 percent change
|
-33.31 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change - SE, overall n=66, 59
|
-28.70 percent change
|
-35.53 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change + SE, males n=30, 32
|
-15.44 percent change
|
-21.18 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change, males n=30, 32
|
-20.35 percent change
|
-25.34 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change - SE, males n=30, 32
|
-24.97 percent change
|
-29.27 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change + SE, males n=30, 32
|
-12.22 percent change
|
-21.97 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change - SE, males n=30, 32
|
-21.62 percent change
|
-29.57 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change + SE, males n=26, 29
|
-16.27 percent change
|
-26.59 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change, males n=26, 29
|
-20.50 percent change
|
-30.05 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change - SE, males n=26, 29
|
-24.51 percent change
|
-33.35 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change + SE, females n=42, 32
|
-24.30 percent change
|
-23.20 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change, females n=42, 32
|
-28.11 percent change
|
-27.60 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change - SE, females n=42, 32
|
-31.74 percent change
|
-31.74 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change + SE, females n=42, 32
|
-22.54 percent change
|
-24.09 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change, females n=42, 32
|
-26.75 percent change
|
-28.77 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change - SE, females n=42, 32
|
-30.73 percent change
|
-33.17 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change + SE, females n=40, 30
|
-26.82 percent change
|
-31.60 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change - SE, females n=40, 30
|
-33.48 percent change
|
-38.66 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change + SE, premenopausal females n=19, 10
|
-13.89 percent change
|
-23.69 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change, premenopausal females n=19, 10
|
-19.28 percent change
|
-29.89 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change - SE, premenopausal females n=19, 10
|
-24.33 percent change
|
-35.59 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change + SE, premenopausal females n=19, 10
|
-12.43 percent change
|
-27.74 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change - SE, premenopausal females n=17, 10
|
-34.10 percent change
|
-42.32 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change+ SE, postmenopausal females n=23, 22
|
-29.10 percent change
|
-25.82 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk80 % change, postmenopausal females n=23, 22
|
-34.39 percent change
|
-31.93 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change+ SE, postmenopausal females n=23, 22
|
-27.51 percent change
|
-23.61 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56 % change, postmenopausal females n=23, 22
|
-34.04 percent change
|
-31.20 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk56% change - SE, postmenopausal females n=23, 22
|
-39.99 percent change
|
-38.04 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change+ SE, postmenopausal females n=23, 20
|
-28.14 percent change
|
-32.02 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20 % change, postmenopausal females n=23, 20
|
-32.70 percent change
|
-36.94 percent change
|
|
Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80
Wk20% change - SE, postmenopausal females n=23, 20
|
-36.97 percent change
|
-41.50 percent change
|
Adverse Events
Metformin
Serious events: 27 serious events
Other events: 159 other events
Deaths: 0 deaths
Avandamet
Serious events: 28 serious events
Other events: 145 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Metformin
n=334 participants at risk
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=344 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.60%
2/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.58%
2/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Appendicitis
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Cellulitis
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.58%
2/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Gastroenteritis
|
0.60%
2/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Abdominal abscess
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Arthritis infective
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Infected skin ulcer
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Localized infection
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Staphylococcal infection
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Subcutaneous abscess
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
2.6%
9/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Coronary artery disease
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.58%
2/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Cardiac discomfort
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Myocardial infarction
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Myocardial ischaemia
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Brain stem infarction
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Carotid artery occlusion
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Cerebral infarction
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Cranial neuropathy
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Haemorrhage itracranial
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Syncope
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.58%
2/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.60%
2/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Renal and urinary disorders
Renal colic
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Renal and urinary disorders
Stress urinary incontinence
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Intrevertebral disc protusion
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.58%
2/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Nasal sinus cancer
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Vascular disorders
Varicose vein
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Eye disorders
Angle closure glaucoma
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.00%
0/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.29%
1/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Surgical and medical procedures
Inguinal hernia repair
|
0.30%
1/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
0.00%
0/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
Other adverse events
| Measure |
Metformin
n=334 participants at risk
Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
|
Avandamet
n=344 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
18.9%
63/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
11.9%
41/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Gastrointestinal disorders
Nausea
|
9.0%
30/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
9.0%
31/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Upper respiratort tract infection
|
9.0%
30/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
6.4%
22/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Headache
|
7.8%
26/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
5.5%
19/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Nasopharyngitis
|
7.8%
26/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
5.2%
18/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Nervous system disorders
Dizziness
|
7.2%
24/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
5.5%
19/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.6%
22/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
4.7%
16/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Infections and infestations
Urinary tract infection
|
6.0%
20/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
6.7%
23/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.7%
19/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
7.3%
25/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.7%
19/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
6.4%
22/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
|
General disorders
Oedema peripheral
|
1.2%
4/334 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
4.7%
16/344 • An on therapy adverse event (AE)/serious adverse event (SAE) was defined as an AE/SAE with onset on or after the start date of study medication but not later than two days after the last date of study medication.
SAEs and AEs were collected in the Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER