Trial Outcomes & Findings for Body Weight Effects on Glucophage's Efficacy in Chinese Diagnosed T2DM Patients (NCT NCT00778622)

Last Updated: 2013-08-23

Results Overview

Baseline for HbA1c is defined as that value obtained at screening visit. HbA1c was measured as a percent (%) of hemoglobin; normal range was 4.7 to 6.4% and values were obtained through a central laboratory. The Last Observation Carried Forward (LOCF) data set includes data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

371 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2013-08-23

Participant Flow

Started November 2009, Completed March 2011 at Peking University People's Hospital. Participants diagnosed with Type 2 diabetes mellitus 6 months prior to enrollment; were oral antidiabetic agent naive (either having received no antidiabetic agents or received agents 14 days or less, or received none within a month of enrollment in the study.

Participants had glycosated hemoglobin A1c (HbA1c) screening values greater than, equal to 7.0% and less than, equal to 10.0%. Participants were between the ages of 17 and 80 years of age and Chinese Asian. Screening visit was up to 7 days prior to Day 1 (treatment).

Participant milestones

Participant milestones
Measure	Glucophage XR in Normal Weight Participants Normal weight was defined as body mass index (BMI) greater than, equal to (\>=)18.5 kilogram per meter squared (kg/m\^2) and less than (\<) 24 kg/m\^2. Initial dose of Glucophage extended release (XR) on Day 1 was 500 mg taken once daily orally with the evening meal. Drug was titrated up by increments of 500 mg each week to a maximum dose of 2000 mg at Week 4 and for the remaining treatment if the fasting plasma glucose (FPG) was greater than 7.0 mmol/L (126 mg/dL). If the FPG was more than 10.0 mmol/L (greater than 180 mg/dL) at Weeks 4, 8, or 12 and the values were confirmed at a repeated measurement, the participant was discontinued from the treatment. Participants were dosed for a total of 16 weeks.	Glucophage XR in Overweight Participants Overweight was defined as body mass index (BMI) greater than, equal to (\>=) 24 kg/m\^2 and less than (\<) 28 kg/m\^2. Initial dose of Glucophage extended release (XR) on Day 1 was 500 mg taken once daily orally with the evening meal. Drug was titrated up by increments of 500 mg each week to a maximum dose of 2000 mg at Week 4 and for the remaining treatment if the fasting plasma glucose (FPG) was greater than 7.0 mmol/L (126 mg/dL). If the FPG was more than 10.0 mmol/L (greater than 180 mg/dL) at Weeks 4, 8, or 12 and the values were confirmed at a repeated measurement, the participant was discontinued from the treatment. Participants were dosed for a total of 16 weeks	Glucophage XR in Obese Participants Obese was defined as body mass index (BMI) greater than, equal to (\>=) 28 kg/m\^2. Initial dose of Glucophage extended release (XR)on Day 1 was 500 mg taken once daily orally with the evening meal. Drug was titrated up by increments of 500 mg each week to a maximum dose of 2000 mg at Week 4 and for the remaining treatment if the fasting plasma glucose (FPG) was greater than 7.0 mmol/L (126 mg/dL). If the FPG was more than 10.0 mmol/L (greater than 180 mg/dL) at Weeks 4, 8, or 12 and the values were confirmed at a repeated measurement, the participant was discontinued from the treatment. Participants were dosed for a total of 16 weeks
Overall Study STARTED	125	122	124
Overall Study COMPLETED	109	107	109
Overall Study NOT COMPLETED	16	15	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Glucophage XR in Normal Weight Participants Normal weight was defined as body mass index (BMI) greater than, equal to (\>=)18.5 kilogram per meter squared (kg/m\^2) and less than (\<) 24 kg/m\^2. Initial dose of Glucophage extended release (XR) on Day 1 was 500 mg taken once daily orally with the evening meal. Drug was titrated up by increments of 500 mg each week to a maximum dose of 2000 mg at Week 4 and for the remaining treatment if the fasting plasma glucose (FPG) was greater than 7.0 mmol/L (126 mg/dL). If the FPG was more than 10.0 mmol/L (greater than 180 mg/dL) at Weeks 4, 8, or 12 and the values were confirmed at a repeated measurement, the participant was discontinued from the treatment. Participants were dosed for a total of 16 weeks.	Glucophage XR in Overweight Participants Overweight was defined as body mass index (BMI) greater than, equal to (\>=) 24 kg/m\^2 and less than (\<) 28 kg/m\^2. Initial dose of Glucophage extended release (XR) on Day 1 was 500 mg taken once daily orally with the evening meal. Drug was titrated up by increments of 500 mg each week to a maximum dose of 2000 mg at Week 4 and for the remaining treatment if the fasting plasma glucose (FPG) was greater than 7.0 mmol/L (126 mg/dL). If the FPG was more than 10.0 mmol/L (greater than 180 mg/dL) at Weeks 4, 8, or 12 and the values were confirmed at a repeated measurement, the participant was discontinued from the treatment. Participants were dosed for a total of 16 weeks	Glucophage XR in Obese Participants Obese was defined as body mass index (BMI) greater than, equal to (\>=) 28 kg/m\^2. Initial dose of Glucophage extended release (XR)on Day 1 was 500 mg taken once daily orally with the evening meal. Drug was titrated up by increments of 500 mg each week to a maximum dose of 2000 mg at Week 4 and for the remaining treatment if the fasting plasma glucose (FPG) was greater than 7.0 mmol/L (126 mg/dL). If the FPG was more than 10.0 mmol/L (greater than 180 mg/dL) at Weeks 4, 8, or 12 and the values were confirmed at a repeated measurement, the participant was discontinued from the treatment. Participants were dosed for a total of 16 weeks
Overall Study Adverse Event	5	4	7
Overall Study Withdrawal by Subject	4	5	5
Overall Study Lost to Follow-up	3	3	2
Overall Study Protocol Violation	0	3	0
Overall Study Lack of Efficacy	2	0	0
Overall Study immigration	1	0	0
Overall Study Other	1	0	1

Baseline Characteristics

Body Weight Effects on Glucophage's Efficacy in Chinese Diagnosed T2DM Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glucophage XR in Normal Weight Participants n=125 Participants Normal weight was defined as body mass index (BMI) greater than, equal to 18.5 kg/m\^2 and \< 24 kg/m\^2 ). Glucophage XR titrated from Day 1 to Week 4 in increments of 500 mg up to maximum dose of 2000 mg. Participants were dosed for a total of 16 weeks.	Glucophage XR in Overweight Participants n=122 Participants Overweight was defined as body mass index (BMI) greater than, equal to 24 kg/m\^2 and less than 28 kg/m\^2. Glucophage XR titrated from Day 1 to Week 4 in increments of 500 mg up to maximum dose of 2000 mg. Participants were dosed for a total of 16 weeks.	Glucophage XR in Obese Participants n=124 Participants Obese was defined as body mass index (BMI) greater than, equal to 28 kg/m\^2. Glucophage XR titrated from Day 1 to Week 4 in increments of 500 mg up to maximum dose of 2000 mg. Participants were dosed for a total of 16 weeks.	Total n=371 Participants Total of all reporting groups
Age Continuous	53.0 years FULL_RANGE 10.32 • n=93 Participants	51.0 years FULL_RANGE 9.21 • n=4 Participants	52.5 years FULL_RANGE 10.97 • n=27 Participants	52.0 years FULL_RANGE 10.17 • n=483 Participants
Sex: Female, Male Female	64 Participants n=93 Participants	45 Participants n=4 Participants	52 Participants n=27 Participants	161 Participants n=483 Participants
Sex: Female, Male Male	61 Participants n=93 Participants	77 Participants n=4 Participants	72 Participants n=27 Participants	210 Participants n=483 Participants
Region of Enrollment China	125 participants n=93 Participants	122 participants n=4 Participants	124 participants n=27 Participants	371 participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set included participants who were enrolled, took at least 1 study medication and had at least 1 post baseline HbA1c assessment. Baseline data was not carried forward or averaged with on-treatment data to impute missing values for the LOCF data set.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=111 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=111 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=112 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Glycosated Hemoglobin A1c (HbA1c) (Last Observation Carried Forward) - Full Analysis Set (FAS)	-1.95 percentage of hemoglobin 95% Confidence Interval 0.922 • Interval -2.12 to -1.77	-1.79 percentage of hemoglobin 95% Confidence Interval 0.941 • Interval -1.96 to -1.61	-1.68 percentage of hemoglobin 95% Confidence Interval 0.854 • Interval -1.83 to -1.52

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) included enrolled participants,who took at least 1 dose of drug and had at least 1 post baseline HbA1c assessment. For this outcome measure, 1, 1, and 1 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

Baseline was defined as the value obtained at the screening visit. FPG was measured in millimoles/Liter (mmol/L) and obtained through local laboratories.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=110 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=110 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=111 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) of Fasting Plasma Glucose (FPG) - Full Analysis Set	-1.979 mmol/L 95% Confidence Interval 1.7877 • Interval -2.317 to -1.641	-2.171 mmol/L 95% Confidence Interval 2.1222 • Interval -2.572 to -1.77	-2.141 mmol/L 95% Confidence Interval 2.0287 • Interval -2.522 to -1.759

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) consisted of participants who were enrolled, took at least 1 study medication and had at least 1 post baseline HbA1c assessment. For this outcome measure, 1, 3, and 8 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

For fasting total cholesterol (TC), baseline is defined as Day 1 (first day of treatment). Total cholesterol was measured in millimoles per liter (mmol/L) and obtained through local laboratories.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=110 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=108 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=104 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Total Cholesterol (TC) - Full Analysis Set	-0.388 mmol/L 95% Confidence Interval 0.9164 • Interval -0.561 to -0.214	-0.048 mmol/L 95% Confidence Interval 0.9560 • Interval -0.231 to 0.134	-0.144 mmol/L 95% Confidence Interval 0.8188 • Interval -0.304 to 0.015

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) consisted of participants who were enrolled, took at least 1 study medication and had at least 1 post baseline HbA1c assessment. For this outcome measure, 1, 3, and 9 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

Baseline was defined as values obtained on Day 1. Low-density lipoprotein cholesterol (LDL-C) was measured in millimoles per liter (mmol/L) and obtained through local laboratories.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=110 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=108 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=103 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Low-density Lipoprotein Cholesterol (LDL-C) - Full Analysis Set	-0.306 mmol/L 95% Confidence Interval 0.5746 • Interval -0.415 to -0.198	-0.143 mmol/L 95% Confidence Interval 0.6605 • Interval -0.269 to -0.017	-0.181 mmol/L 95% Confidence Interval 0.6258 • Interval -0.303 to -0.059

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) consisted of participants who were enrolled, took at least 1 study medication and had at least 1 post baseline HbA1c assessment. For this outcome measure, 2, 3, and 8 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

Baseline was defined as value obtained on Day 1 (first day of treatment). High-density lipoprotein cholesterol (HDL-C) was measured in millimoles per liter (mmol/L) and obtained through local laboratories.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=109 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=108 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=104 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting High-density Lipoprotein Cholesterol (HDL-C) - Full Analysis Set	0.056 mmol/L 95% Confidence Interval 0.2016 • Interval 0.017 to 0.094	0.024 mmol/L 95% Confidence Interval 0.3428 • Interval -0.042 to 0.089	0.032 mmol/L 95% Confidence Interval 0.2042 • Interval -0.007 to 0.072

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) consisted of participants who were enrolled, took at least 1 study medication and had at least 1 post baseline HbA1c assessment. For this outcome measure, 1, 4, and 8 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

Baseline was defined as value obtained on Day 1 (first day of treatment). Triglycerides (TG) were measured in millimoles per liter (mmol/L)and values obtained through local laboratories.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=110 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=107 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=104 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Triglycerides (TG) - Full Analysis Set	-0.172 mmol/L 95% Confidence Interval 2.0678 • Interval -0.563 to 0.219	0.262 mmol/L 95% Confidence Interval 3.3195 • Interval -0.374 to 0.898	-0.041 mmol/L 95% Confidence Interval 2.2018 • Interval -0.47 to 0.387

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) consisted of participants who were enrolled, took at least 1 study medication and had at least 1 post baseline HbA1c assessment. For this outcome measure, 102, 95, and 85 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

Baseline was defined as value obtained on Day 1 (first day of treatment). C-Reactive Protein (CRP) was measured in milligrams/liter (mg/L) and values were obtained through a central laboratory; normal was less than 5.0 mg/L.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=9 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=16 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=27 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in C-Reactive Protein (CRP) - Full Analysis Set	-0.589 mg/L 95% Confidence Interval 1.0914 • Interval -1.428 to 0.25	3.144 mg/L 95% Confidence Interval 16.4019 • Interval -5.596 to 11.884	1.633 mg/L 95% Confidence Interval 8.0706 • Interval -1.559 to 4.826

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) population = 111, 111, 112 in normal, overweight, obese participants respectively. For this outcome measure, 84, 79, and 75 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

Baseline was defined as value obtained on Day 1 (first day of treatment). PAI-1 (activity) was measured in units/milliliter (U/mL)and values obtained through a central laboratory; normal was less than 25.00 U/mL.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=27 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=32 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=37 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Plasminogen Activator Inhibitor-1 (PAI-1) - Full Analysis Set	0.465 U/mL 95% Confidence Interval 8.5233 • Interval -2.907 to 3.837	1.177 U/mL 95% Confidence Interval 8.9405 • Interval -2.047 to 4.4	-1.792 U/mL 95% Confidence Interval 7.9231 • Interval -4.434 to 0.849

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full Analysis Set (FAS) included participants who were enrolled, took at least 1 study medication and had at least 1 post baseline HbA1c assessment. For this outcome measure, 78, 70, and 72 normal, overweight, obese participants, respectively, were missing and were not included in the analysis.

Baseline was defined as value obtained on Day 1 (first day of treatment). Adiponectin was measured in milligrams/liter (mg/L) and values obtained through a central laboratory; normal range was 1.20 to 20.00 mg/L.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=33 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=41 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=40 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Adiponectin - Full Analysis Set	1.742 mg/L 95% Confidence Interval 8.6503 • Interval -1.325 to 4.81	1.102 mg/L 95% Confidence Interval 2.2116 • Interval 0.404 to 1.801	0.050 mg/L 95% Confidence Interval 3.5516 • Interval -1.086 to 1.186

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Week 16

Population: All participants enrolled in the study and who received at least 1 dose of Glucophage XR.

Day 1 was first day of treatment. Lactic acidosis defined as elevated blood lactate levels (\>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and increased lactate/pyruvate ratio. Hypoglycemia (low levels of blood glucose) was reported as an adverse event. Safety population included participants who had enrolled in the study and took at least 1 dose of glucophage extended release (glucophage XR). If a subject experienced more than one adverse event, the subject was counted once at the highest severity.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=125 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=122 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=124 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Number of Participants With Episodes of Lactic Acidosis or Hypoglycemia From Day 1 to Week 16 - Safety Population Lactic Acidosis	0 participants	0 participants	0 participants
Number of Participants With Episodes of Lactic Acidosis or Hypoglycemia From Day 1 to Week 16 - Safety Population Hypoglycemia	1 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Population: Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.

Hematology profile = hematocrit, hemoglobin, red blood cell count (RBC), white blood cell count(WBC), lymphocytes, monocytes, basophils, eosinophils, neutrophils, platelet count. Baseline: value obtained at screening or last value obtained before treatment. LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Hemoglobin (g/dL): \>3 g/dL decrease from preRX; hematocrit (%): \<0.75\*preRX; RBC (\*10\^6 c/uL): \<0.75\*preRX; platelet count (\*10\^9 c/uL): \<0.67\*LLN or \>1.5\*ULN, of if preRX\<LLN, use 0.5\*preRX and \<100,000/mm\^3; WBC (\*10\^3 c/uL): \<0.75\*LLN or \>1.25\*ULN, or if preRX \<LLN, use \<0.8\*preRX or \>ULN, or if preRX\>ULN, use \>1.2\*preRX or \<LLN; neutrophils+bands (\*10\^3 c/uL): if value \<1.0\*10\^3 c/uL; eosinophils (\*10\^3 c/uL): if value \>0.750\*10\^3 c/uL; basophils (\*10\^3 c/uL): if value \>400/mm\^3; monocytes (\*10\^3 c/uL): if value \>2000/mm\^3; lymphocytes (\*10\^3 c/uL): if value \<0.750\*10\^3 c/uL or if value \>7.50\*10\^3 c/uL.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=125 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=122 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=124 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Number of Participants With Clinically Significant Changes From Baseline at Week 16 in the Hematology Laboratory Test Profile - Safety Population	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Population: Number of participants (normal, overweight, obese, respectively) who were missing values and were not included in the Week 16 analysis for the following serum chemistry tests: ALT = 14, 11, 13; AST = 14, 11, 13; total BR = 14, 11, 13; creatinine = 14, 12, 13; BUN = 14, 12, 13; UA = 14, 12, 13.

Baseline defined as value obtained either in screening visit or last value obtained before glucophage XR treatment given on Day 1. Serum chemistries evaluating kidney or liver function: blood urea nitrogen(BUN), serum creatinine (SCr), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin (BR), uric acid (UA). Abnormal increase in kidney and liver function tests defined as 1.25 - less than, equal to (\<=)2.6 times (x) upper limit of normal (ULN)in ALT, AST, total BR, UA; abnormal increase defined as 1.25 to \<= 5.1 x ULN in BUN. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=125 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=122 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=124 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 ALT 1.25 to <= 2.6xULN	2 participants	11 participants	9 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 ALT > 2.6 x ULN	0 participants	0 participants	0 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 AST 1.25 to <= 2.6xULN	0 participants	5 participants	4 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 AST > 2.6 x ULN	0 participants	0 participants	0 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 Total BR 1.25 to <=2.6xULN	3 participants	2 participants	1 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 Total BR > 2.6 x ULN	0 participants	0 participants	0 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 BUN1.25 to <=5.1xULN	0 participants	1 participants	0 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 BUN > 5.1 x ULN	0 participants	0 participants	0 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 UA 1.25 to <=2.6xULN	3 participants	5 participants	7 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 UA > 2.6 x ULN	0 participants	0 participants	0 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 SCr 1.25 to <=2.6xULN	0 participants	0 participants	0 participants
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population Number with Week 16 SCr > 1.25 x ULN	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Urinalysis included pH and specific gravity. Baseline defined as values obtained at screening visit. Clinically significant: outside the reference range (low/high)and judged to be significant by the investigator: Specific gravity 1.003 - 1.035; ph 5 - 8. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=125 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=122 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=124 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Number of Participants With Clinically Significant Changes From Baseline at Week 16 in Urinalysis - Safety Population	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Population: Safety population included 125, 122, 124 participants in each arm, respectively. Participants missing from analysis for change at Week 16 for Heart Rate were 17, 18, 20 participants in the normal, overweight, obese arms, respectively.

Baseline was defined as ECG obtained at the screening visit. ECG was 12-lead. Heart rate (HR) was measured in beats per minute (beats/min). Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=108 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=104 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=104 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week at Week 16 in ECG Parameter Heart Rate (HR) - Safety Population	0.4 beats/min Standard Deviation 8.91	1.2 beats/min Standard Deviation 9.56	1.1 beats/min Standard Deviation 12.36

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Baseline was defined as the value obtained at screening or value obtained on Day 1 before treatment. Diastolic and systolic blood pressure was measured in millimeters of mercury (mm Hg). Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=125 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=122 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=124 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Mean Change From Baseline at Week 16 in Diastolic and Systolic Blood Pressure - Safety Population Week 16 change in diastolic blood pressure	-2.2 mm Hg Standard Deviation 8.63	-4.1 mm Hg Standard Deviation 9.31	-1.4 mm Hg Standard Deviation 9.37
Mean Change From Baseline at Week 16 in Diastolic and Systolic Blood Pressure - Safety Population Week 16 change in systolic blood pressure	-4.6 mm Hg Standard Deviation 14.21	-5.5 mm Hg Standard Deviation 12.14	-1.7 mm Hg Standard Deviation 14.55

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 16

Population: number of participants with a normal ECG at baseline for normal weight, overweight, and obese arms were 71, 62, 65, respectively.

Baseline was defined as ECG obtained at the screening visit. A judgment of clinical significance was at the discretion of the investigator. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.

Outcome measures

Outcome measures
Measure	Glucophage XR in Normal Weight Participants n=125 Participants Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 .	Glucophage XR in Overweight Participants n=122 Participants Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=124 Participants Obese was defined as BMI \>= 28 kg/m\^2.
Number of Participants Who Had a Normal Electrocardiogram (ECG) at Baseline and an ECG at Week 16 (or Termination Visit) Which Was Considered to be Abnormal With Clinical Significance - Safety Population	0 participants	1 participants	3 participants

Adverse Events

Glucophage XR in Normal Weight Participants

Serious events: 1 serious events

Other events: 43 other events

Deaths: 0 deaths

Glucophage XR in Overweight Participants

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

Glucophage XR in Obese Participants

Serious events: 1 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Glucophage XR in Normal Weight Participants n=125 participants at risk Normal weight defined as BMI \>= 18.5 kg/m\^2 and \< 24 kg/m\^2 ).	Glucophage XR in Overweight Participants n=122 participants at risk Overweight defined as BMI \>= 24 kg/m\^2 and \< 28 kg/m\^2.	Glucophage XR in Obese Participants n=124 participants at risk Obese was defined as BMI \>= 28 kg/m\^2.
Respiratory, thoracic and mediastinal disorders Right upper lung cancer	0.80% 1/125 • Number of events 1 • 16 Weeks A treatment-emergent AE (TEAE) was defined as an event that occurs during the treatment period.	0.00% 0/122 • 16 Weeks A treatment-emergent AE (TEAE) was defined as an event that occurs during the treatment period.	0.00% 0/124 • 16 Weeks A treatment-emergent AE (TEAE) was defined as an event that occurs during the treatment period.
Blood and lymphatic system disorders Hypertension	0.00% 0/125 • 16 Weeks A treatment-emergent AE (TEAE) was defined as an event that occurs during the treatment period.	0.00% 0/122 • 16 Weeks A treatment-emergent AE (TEAE) was defined as an event that occurs during the treatment period.	0.81% 1/124 • Number of events 1 • 16 Weeks A treatment-emergent AE (TEAE) was defined as an event that occurs during the treatment period.

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER