Type 2 Diabetes Mellitus
Conditions
Brief summary
The incidence of type 2 diabetes is on the increase. According to recent Canadian Diabetes Association guidelines glucose control, based on the A1C measurement, needs to be achieved within a 6-12 month period of time after the initial diagnosis of type 2 diabetes. The guidelines on the use of antihyperglycemic agents identify the potential benefits of sub-maximal oral combination therapy in order to achieve more rapid and improved glycemic control compared with higher dose monotherapy. Furthermore, many patients on prolonged oral antihyperglycemic monotherapy who then start on combination therapy may not achieve the required target glycemic control. Indeed early initiation of combination therapies may be necessary to achieve and maintain glycemic targets because of the progressive deterioration of pancreatic β cell function and glycemic control.
Detailed description
AvandametTM combines two oral antihyperglycemic agents, rosiglitazone maleate and metformin hydrochloride, with different but complementary mechanisms of action to improve glycemic control while reducing circulating insulin levels in patients with type 2 diabetes. AvandiaTM and AmarylTM combine two antidiabetic agents, rosiglitazone maleate and glimepiride. Glimepiride is an effective antihyperglycemic agent which has a low incidence of hypoglycemia, symptomatic hypoglycemia, severe hypoglycemia, and confirmed hypoglycemia. Subjects in this study who are inadequately controlled on diet, exercise and a submaximal dose of metformin or sulfonylurea (SU) will be randomized to either a combination of metformin plus rosiglitazone (AvandametTM) or a combination of AvandiaTM + AmarylTM or a Metformin monotherapy arm. As per the Canadian Diabetes Association (CDA) guidelines, their fasting plasma glucose and A1C to be 7 (mmol/L / percent) or less throughout the study. If the subject does not achieve the target then either AvandametTM or AvandiaTM and AmarylTM or Metformin will be up-titrated in an effort to reach this CDA recommended target. This study will attempt to demonstrate that the either combination arm of rosiglitazone plus metformin (AvandametTM) or the other combination arm of AvandiaTM + AmarylTM will provide greater glycemic control while avoiding the side-effects associated with the use of maximal dose metformin.
Interventions
DRUGAvandamet
Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily compared to Avandia 4 mg and Amaryl 1 mg once daily over 6 months or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.
DRUGAvandia and Amaryl
Avandia 4 mg and Amaryl 1 mg once daily compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily, or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.
DRUGMetformin
Metformin 500 mg twice daily up to 1000 mg over 6 months compared to Avandia 4 mg and Amaryl 1 mg once daily or compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily
Sponsors
GlaxoSmithKline
Canadian Heart Research Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Type 2 diabetes patients 2. 18 - 75 years old 3. Type 2 diabetes mellitus (DM) drug naïve or on submaximal oral monotherapy \< 3 years 4. A1C criteria at screening: 1. 7.1-10% for drug naïve patients after failure of diet control and life-style modification 2. 7.1 - 9% on single therapy (e.g. not more 10 mg of Glyburide or 4 mg of Amaryl™ or 1000mg of Metformin) who will start after 2 weeks wash-out. During wash out the following will be done: i) diet and life style modification ii) Angiotensin converting enzyme inhibitor (ACE), aspirin (80 mg), and statin if appropriate 5. Signed informed consent
Exclusion criteria
1. Type 1 diabetes 2. Subjects currently treated with insulin 3. Subject treated for previous 3 month with any thiazolidinedione (TZD) 4. Evidence of clinically significant concomitant illnesses which are not controlled by medication and/or may limit participation in the study as judged by the investigator 5. Subjects who have hypersensitivity to any components of study drugs 6. Participation in a clinical trial and/or intake of an investigational drug within 30 days prior to screening. 7. Pregnant or nursing females 8. Females of childbearing potential who are not on adequate birth control 9. Liver enzymes (Alanine Aminotransferase (ALT) \> 2.5 times upper limit of normal) 10. Renal impairment: serum creatinine ≥ 136umol/L (males) and ≥ 124 umol/L (females) 11. Congestive Heart Failure (CHF class III/IV) 12. Weight \>160 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in A1C at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the Month 6 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in A1C at Month 12 | Baseline and Month 12 | Change from baseline was calculated as the Month 12 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values. |
| Number of Subjects Achieving A1C Target at Month 4 | Month 4 | A1C responders were described as subjects having achieved A1C less than 7 percent at Month 4, with LOCF from Month 2. |
| Number of Subjects Achieving A1C Target at Month 6 | Month 6 | A1C responders were described as subjects having achieved A1C less than 7 percent at Month 6, with LOCF from Month 2. |
| Number of Subjects Achieving A1C Target at Month 12 | Month 12 | A1C responders were described as subjects having achieved A1C less than 7 percent at Month 12 with LOCF from Month 2. |
| Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4 | Baseline and Month 4 | Change from baseline was calculated as the Month 4 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values. |
| Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the Month 6 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values. |
| Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12 | Baseline and Month 12 | Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 2 for withdrawn subjects or missing values. |
| Number of Subjects Achieving FPG Target at Month 4 | Month 4 | FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 4 with LOCF from Month 2. |
| Mean Change From Baseline in A1C at Month 4 | Baseline and Month 4 | Change from baseline was calculated as the Month 4 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values. |
| Number of Subjects Achieving FPG Target at Month 12 | Month 12 | FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 12 with LOCF from Month 2. |
| Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the Month 6 value minus the baseline value, with LOCF from Month 2. The UKPDS (United Kingdom Prospective Diabetes Study) risk engine calculated was based on 5 years risk using gender, race, age at diagnosis of diabetes, duration of diabetes, smoking status, A1C, systolic blood pressure and total cholesterol to high-density lipoprotein (HDL) ratio at a specified visit. The UKPDS cardiovascular disease (CVD) risk engine is used to estimate the risk of having coronary heart disease in type II diabetes according to the UKPDS model. The possible risk scores can range from 0 to 100% and hence lower scores would predict a person is less likely to have an event. |
| Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12 | Baseline and Month 12 | Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 2. The UKPDS (U.K. Prospective Diabetes Study) risk engine calculated was based on 5 years risk using gender, race, age at diagnosis of diabetes, duration of diabetes, smoking status, A1C, systolic blood pressure and total cholesterol to HDL ratio at a specified visit. The UKPDS cardiovascular disease (CVD) risk engine is used to estimate the risk of having coronary heart disease in type II diabetes according to the UKPDS model. The possible risk scores can range from 0 to 100% and hence lower scores would predict a person is less likely to have an event. |
| Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the Month 6 value minus the baseline value. LOCF was not used for this analysis. CRP was only done at baseline, months 6 and 8. The test was optional and performed only by participating sites. |
| Mean Change From Baseline in C-reactive Protein (CRP) at Month 12 | Baseline and Month 12 | Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 6. CRP was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites. |
| Mean Change From Baseline in Adiponectin at Month 6 | Baseline and Month 6 | Change from baseline was calculated as the Month 6 value minus the baseline value. LOCF was not used for this analysis. Adiponectin was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites. |
| Mean Change From Baseline in Adiponectin at Month 12 | Baseline and Month 12 | Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 6. Adiponectin was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites. |
| Number of Subjects Achieving FPG Target at Month 6 | Month 6 | FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 6 with LOCF from Month 2. |
Countries
Canada
Participant flow
Recruitment details
391 patients were randomized from 49 Canadian sites of General Practitioners and Community Endocrinologists during an 8 month recruitment period.
Pre-assignment details
This open-label, prospective, randomized multi-centre study included naïve or recently treated type 2 diabetes mellitus (T2DM) patients. Recently treated patients (up to 3 years on single therapy of a low to moderate dose of Glyburide or Amaryl™ or Metformin) entered the study after a 2-week wash-out period.
Participants by arm
| Arm | Count |
|---|---|
| Avandia and Amaryl 4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months | 136 |
| Avandamet 2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months | 135 |
| Metformin 500 mg twice daily titration up to 1000 mg twice daily over 6 months | 120 |
| Total | 391 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Period (First 6 Months) | Administrative reasons | 2 | 0 | 5 | 0 | 0 | 0 |
| First Period (First 6 Months) | Adverse Event | 9 | 4 | 5 | 0 | 0 | 0 |
| First Period (First 6 Months) | Clinically significant lab abnormalities | 1 | 2 | 0 | 0 | 0 | 0 |
| First Period (First 6 Months) | Death | 0 | 1 | 0 | 0 | 0 | 0 |
| First Period (First 6 Months) | Lost to Follow-up | 7 | 3 | 3 | 0 | 0 | 0 |
| First Period (First 6 Months) | Protocol Violation | 2 | 2 | 1 | 0 | 0 | 0 |
| First Period (First 6 Months) | Withdrawal by Subject | 4 | 6 | 2 | 0 | 0 | 0 |
| Second Period (Additional Drug Added) | Administrative reasons | 4 | 2 | 0 | 0 | 1 | 0 |
| Second Period (Additional Drug Added) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 1 |
| Second Period (Additional Drug Added) | Clinically significant lab abnormalities | 0 | 0 | 0 | 1 | 0 | 0 |
| Second Period (Additional Drug Added) | Lost to Follow-up | 3 | 0 | 2 | 1 | 0 | 2 |
| Second Period (Additional Drug Added) | Protocol Violation | 0 | 1 | 1 | 0 | 0 | 0 |
| Second Period (Additional Drug Added) | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Avandia and Amaryl | Avandamet | Metformin | Total |
|---|---|---|---|---|
| Age Continuous | 54.3 years STANDARD_DEVIATION 10.1 | 53.7 years STANDARD_DEVIATION 11.6 | 56.0 years STANDARD_DEVIATION 10.1 | 54.6 years STANDARD_DEVIATION 10.7 |
| Region of Enrollment Canada | 136 participants | 135 participants | 120 participants | 391 participants |
| Sex: Female, Male Female | 48 Participants | 59 Participants | 57 Participants | 164 Participants |
| Sex: Female, Male Male | 88 Participants | 76 Participants | 63 Participants | 227 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 136 | 3 / 117 | 0 / 104 |
| serious Total, serious adverse events | 0 / 136 | 0 / 135 | 0 / 120 |
Outcome results
Primary
Mean Change From Baseline in A1C at Month 6
Change from baseline was calculated as the Month 6 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Time frame: Baseline and Month 6
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with a value at baseline and at Month 6 were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in A1C at Month 6 | Baseline | 8.14 percent | Standard Error 0.095 |
| Avandia and Amaryl | Mean Change From Baseline in A1C at Month 6 | Change from baseline | -1.61 percent | Standard Error 0.108 |
| Avandamet | Mean Change From Baseline in A1C at Month 6 | Change from baseline | -1.39 percent | Standard Error 0.081 |
| Avandamet | Mean Change From Baseline in A1C at Month 6 | Baseline | 7.96 percent | Standard Error 0.076 |
| Metformin | Mean Change From Baseline in A1C at Month 6 | Change from baseline | -1.02 percent | Standard Error 0.092 |
| Metformin | Mean Change From Baseline in A1C at Month 6 | Baseline | 7.90 percent | Standard Error 0.085 |
Secondary
Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 2. The UKPDS (U.K. Prospective Diabetes Study) risk engine calculated was based on 5 years risk using gender, race, age at diagnosis of diabetes, duration of diabetes, smoking status, A1C, systolic blood pressure and total cholesterol to HDL ratio at a specified visit. The UKPDS cardiovascular disease (CVD) risk engine is used to estimate the risk of having coronary heart disease in type II diabetes according to the UKPDS model. The possible risk scores can range from 0 to 100% and hence lower scores would predict a person is less likely to have an event.
Time frame: Baseline and Month 12
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12 | -0.72 percent | Standard Error 0.392 |
| Avandamet | Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12 | -0.62 percent | Standard Error 0.252 |
| Metformin | Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12 | -1.11 percent | Standard Error 0.234 |
Secondary
Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6
Change from baseline was calculated as the Month 6 value minus the baseline value, with LOCF from Month 2. The UKPDS (United Kingdom Prospective Diabetes Study) risk engine calculated was based on 5 years risk using gender, race, age at diagnosis of diabetes, duration of diabetes, smoking status, A1C, systolic blood pressure and total cholesterol to high-density lipoprotein (HDL) ratio at a specified visit. The UKPDS cardiovascular disease (CVD) risk engine is used to estimate the risk of having coronary heart disease in type II diabetes according to the UKPDS model. The possible risk scores can range from 0 to 100% and hence lower scores would predict a person is less likely to have an event.
Time frame: Baseline and Month 6
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6 | -1.09 percent | Standard Error 0.246 |
| Avandamet | Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6 | -1.05 percent | Standard Error 0.169 |
| Metformin | Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6 | -1.54 percent | Standard Error 0.234 |
Secondary
Mean Change From Baseline in A1C at Month 12
Change from baseline was calculated as the Month 12 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Time frame: Baseline and Month 12
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in A1C at Month 12 | -1.50 percent | Standard Error 0.115 |
| Avandamet | Mean Change From Baseline in A1C at Month 12 | -1.56 percent | Standard Error 0.086 |
| Metformin | Mean Change From Baseline in A1C at Month 12 | -1.14 percent | Standard Error 0.111 |
Secondary
Mean Change From Baseline in A1C at Month 4
Change from baseline was calculated as the Month 4 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Time frame: Baseline and Month 4
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in A1C at Month 4 | -1.44 percent | Standard Error 0.099 |
| Avandamet | Mean Change From Baseline in A1C at Month 4 | -1.28 percent | Standard Error 0.083 |
| Metformin | Mean Change From Baseline in A1C at Month 4 | -0.94 percent | Standard Error 0.097 |
Secondary
Mean Change From Baseline in Adiponectin at Month 12
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 6. Adiponectin was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites.
Time frame: Baseline and Month 12
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in Adiponectin at Month 12 | 4.95 µg/mL | Standard Error 0.902 |
| Avandamet | Mean Change From Baseline in Adiponectin at Month 12 | 8.21 µg/mL | Standard Error 1.804 |
| Metformin | Mean Change From Baseline in Adiponectin at Month 12 | 1.453 µg/mL | Standard Error 0.371 |
Secondary
Mean Change From Baseline in Adiponectin at Month 6
Change from baseline was calculated as the Month 6 value minus the baseline value. LOCF was not used for this analysis. Adiponectin was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites.
Time frame: Baseline and Month 6
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in Adiponectin at Month 6 | 5.73 microgram per millilitre (µg/mL) | Standard Error 0.869 |
| Avandamet | Mean Change From Baseline in Adiponectin at Month 6 | 6.37 microgram per millilitre (µg/mL) | Standard Error 1.453 |
| Metformin | Mean Change From Baseline in Adiponectin at Month 6 | 0.23 microgram per millilitre (µg/mL) | Standard Error 0.299 |
Secondary
Mean Change From Baseline in C-reactive Protein (CRP) at Month 12
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 6. CRP was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites.
Time frame: Baseline and Month 12
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in C-reactive Protein (CRP) at Month 12 | -0.40 mg/dL | Standard Deviation 0.323 |
| Avandamet | Mean Change From Baseline in C-reactive Protein (CRP) at Month 12 | -1.52 mg/dL | Standard Deviation 0.642 |
| Metformin | Mean Change From Baseline in C-reactive Protein (CRP) at Month 12 | -1.52 mg/dL | Standard Deviation 0.817 |
Secondary
Mean Change From Baseline in C-reactive Protein (CRP) at Month 6
Change from baseline was calculated as the Month 6 value minus the baseline value. LOCF was not used for this analysis. CRP was only done at baseline, months 6 and 8. The test was optional and performed only by participating sites.
Time frame: Baseline and Month 6
Population: All Primary and secondary endpoints were calculated on the Intent to Treat (ITT) population where each patient had at least one dose of the medication and at least one valid observation. Missing values were carried forward (using Last Observation Carried Forward method) except for the calculation of the composite variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 | -1.20 milligram per decilitre (mg/dL) | Standard Error 0.419 |
| Avandamet | Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 | -1.68 milligram per decilitre (mg/dL) | Standard Error 0.64 |
| Metformin | Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 | -1.25 milligram per decilitre (mg/dL) | Standard Error 0.804 |
Secondary
Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 2 for withdrawn subjects or missing values.
Time frame: Baseline and Month 12
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12 | -2.71 millimoles per litre (mmol/L) | Standard Error 0.274 |
| Avandamet | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12 | -2.76 millimoles per litre (mmol/L) | Standard Error 0.225 |
| Metformin | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12 | -2.12 millimoles per litre (mmol/L) | Standard Error 0.231 |
Secondary
Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4
Change from baseline was calculated as the Month 4 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Time frame: Baseline and Month 4
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4 | -2.86 millimoles per litre (mmol/L) | Standard Error 0.247 |
| Avandamet | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4 | -2.33 millimoles per litre (mmol/L) | Standard Error 0.181 |
| Metformin | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4 | -1.75 millimoles per litre (mmol/L) | Standard Error 0.204 |
Secondary
Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6
Change from baseline was calculated as the Month 6 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Time frame: Baseline and Month 6
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avandia and Amaryl | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6 | -2.98 millimoles per litre (mmol/L) | Standard Error 0.259 |
| Avandamet | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6 | -2.55 millimoles per litre (mmol/L) | Standard Error 0.2 |
| Metformin | Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6 | -1.86 millimoles per litre (mmol/L) | Standard Error 0.192 |
Secondary
Number of Subjects Achieving A1C Target at Month 12
A1C responders were described as subjects having achieved A1C less than 7 percent at Month 12 with LOCF from Month 2.
Time frame: Month 12
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avandia and Amaryl | Number of Subjects Achieving A1C Target at Month 12 | 95 participants |
| Avandamet | Number of Subjects Achieving A1C Target at Month 12 | 111 participants |
| Metformin | Number of Subjects Achieving A1C Target at Month 12 | 82 participants |
Secondary
Number of Subjects Achieving A1C Target at Month 4
A1C responders were described as subjects having achieved A1C less than 7 percent at Month 4, with LOCF from Month 2.
Time frame: Month 4
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avandia and Amaryl | Number of Subjects Achieving A1C Target at Month 4 | 83 participants |
| Avandamet | Number of Subjects Achieving A1C Target at Month 4 | 96 participants |
| Metformin | Number of Subjects Achieving A1C Target at Month 4 | 69 participants |
Secondary
Number of Subjects Achieving A1C Target at Month 6
A1C responders were described as subjects having achieved A1C less than 7 percent at Month 6, with LOCF from Month 2.
Time frame: Month 6
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline Month 6 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avandia and Amaryl | Number of Subjects Achieving A1C Target at Month 6 | 94 participants |
| Avandamet | Number of Subjects Achieving A1C Target at Month 6 | 98 participants |
| Metformin | Number of Subjects Achieving A1C Target at Month 6 | 69 participants |
Secondary
Number of Subjects Achieving FPG Target at Month 12
FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 12 with LOCF from Month 2.
Time frame: Month 12
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avandia and Amaryl | Number of Subjects Achieving FPG Target at Month 12 | 64 participants |
| Avandamet | Number of Subjects Achieving FPG Target at Month 12 | 86 participants |
| Metformin | Number of Subjects Achieving FPG Target at Month 12 | 51 participants |
Secondary
Number of Subjects Achieving FPG Target at Month 4
FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 4 with LOCF from Month 2.
Time frame: Month 4
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avandia and Amaryl | Number of Subjects Achieving FPG Target at Month 4 | 58 participants |
| Avandamet | Number of Subjects Achieving FPG Target at Month 4 | 65 participants |
| Metformin | Number of Subjects Achieving FPG Target at Month 4 | 38 participants |
Secondary
Number of Subjects Achieving FPG Target at Month 6
FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 6 with LOCF from Month 2.
Time frame: Month 6
Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avandia and Amaryl | Number of Subjects Achieving FPG Target at Month 6 | 61 participants |
| Avandamet | Number of Subjects Achieving FPG Target at Month 6 | 76 participants |
| Metformin | Number of Subjects Achieving FPG Target at Month 6 | 43 participants |