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

The Relationship Between Baseline Body Weight and Glycemic Control Following Metformin Extended-Release Tablets (Glucophage XR) Monotherapy in Chinese Patients With Newly Diagnosed Type 2 Diabetes

The purpose of this study is to investigate the effect of the baseline body mass index (BMI) on the response to Glucophage XR monotherapy in glycemic control in Chinese patients with newly diagnosed type 2 diabetes

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Metformin XR

• Study Type: Interventional
• Enrollment (Actual): 371
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Local Institution
    • Beijing, Beijing, China, 100730
      • Local Institution
    • Beijing, Beijing, China, 100044
      • Local Institution
    • Beijing, Beijing, China, 100028
      • Local Institution
    • Beijing, Beijing, China, 100088
      • Local Institution
    • Beijing, Beijing, China, 101100
      • Local Institution
    • Beijing, Beijing, China, 200016
      • Local Institution
  • Guangdong
    • Guangdong, Guangdong, China, 510180
      • Local Institution
    • Guangdong Province, Guangdong, China, 510180
      • Local Institution
    • Guangdong Province, Guangdong, China, 528000
      • Local Institution
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Local Institution
    • Shanghai, Shanghai, China, 200003
      • Local Institution
    • Shanghai, Shanghai, China, 201100
      • Local Institution
    • Shanghai, Shanghai, China, 201200
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 79 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed Written Informed Consent
• Age≥ 17 and <80 years,
• Newly diagnosed T2DM (defined as T2DM diagnosed within 6 months prior to enrollment)
• Oral antidiabetic agents naïve (defined as without receiving any anti-diabetic medication therapy before, or having received anti-diabetic medication ≤ 14 days but not received any antidiabetic medication within the last 1 month prior to enrollment)
• HbA1c ≥ 7.0% and ≤10.0%

Exclusion Criteria:

• Women of child bearing potential
• body mass index (BMI)≥35 Kg/m2 or BMI <18.5 Kg/m2
• Hemoglobin A1c (HbA1c)>10.0% or <7.0%
• Active liver disease and/or significant abnormal liver function
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma
• Congestive heart failure defined as New York Heart Association (NYHA) class III or IV and /or left ventricular ejection fraction ≤40%
• Significant cardiovascular history with the past 6 months
• Severe retinopathy, persistent uncontrolled hypertension (SBP≥180mmHg, or DBP≥105mmHg)
• Severe chronic gastrointestinal disease
• History of alcohol abuse or illegal drug abuse within the past 12 months
• Diagnosed anemia
• Creatine kinase ≥3 X ULN
• Serum creatinine ≥1.5 mg/dL(133μmol/L) [males], ≥1.4 mg/dL(124 μmol/L)[females]
• Alanine amino transferase (ALT) and/or aspartate amino transferase (AST)> 1.5 X ULN and/or total bilirubin > 2 X ULN
• Hemoglobin <12g/dL [males], <11g/dL [females]
• Allergies and Adverse Drug Reactions
• Prohibited Treatments and/or Therapies
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
• Subjects decline to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1; Normal Weight by Body Weight Index	Drug: Metformin XR; Tablets, Oral, 500mg tid, 1500 mg/day, 16 weeks
Experimental: A2; Overweight by Body Weight Index	Drug: Metformin XR; Tablets, Oral, 500mg tid, 1500 mg/day, 16 weeks
Experimental: A3; Obese by Body Weight Index	Drug: Metformin XR; Tablets, Oral, 500mg tid, 1500 mg/day, 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Glycosated Hemoglobin A1c (HbA1c) (Last Observation Carried Forward) - Full Analysis Set (FAS)	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.	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline at Week 16 (95% Confidence Interval) of Fasting Plasma Glucose (FPG) - Full Analysis Set	Baseline was defined as the value obtained at the screening visit. FPG was measured in millimoles/Liter (mmol/L) and obtained through local laboratories.	Baseline to Week 16
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Total Cholesterol (TC) - Full Analysis Set	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.	Baseline to Week 16
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Low-density Lipoprotein Cholesterol (LDL-C) - Full Analysis Set	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.	Baseline to Week 16
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting High-density Lipoprotein Cholesterol (HDL-C) - Full Analysis Set	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.	Baseline to Week 16
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Triglycerides (TG) - Full Analysis Set	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.	Baseline to Week 16
Mean Change From Baseline at Week 16 (95% Confidence Interval) in C-Reactive Protein (CRP) - Full Analysis Set	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.	Baseline to Week 16
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Plasminogen Activator Inhibitor-1 (PAI-1) - Full Analysis Set	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.	Baseline to Week 16
Mean Change From Baseline at Week 16 (95% Confidence Interval) in Adiponectin - Full Analysis Set	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.	Baseline to Week 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Episodes of Lactic Acidosis or Hypoglycemia From Day 1 to Week 16 - Safety Population	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.	Day 1 to Week 16
Number of Participants With Clinically Significant Changes From Baseline at Week 16 in the Hematology Laboratory Test Profile - Safety Population	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.	Baseline to Week 16
Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population	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.	Baseline to Week 16
Number of Participants With Clinically Significant Changes From Baseline at Week 16 in Urinalysis - Safety Population	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.	Baseline to Week 16
Mean Change From Baseline at Week at Week 16 in ECG Parameter Heart Rate (HR) - Safety Population	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.	Baseline to Week 16
Mean Change From Baseline at Week 16 in Diastolic and Systolic Blood Pressure - Safety Population	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.	Baseline to Week 16
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	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.	Baseline to Week 16

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Ji L, Li H, Guo X, Li Y, Hu R, Zhu Z. Impact of baseline BMI on glycemic control and weight change with metformin monotherapy in Chinese type 2 diabetes patients: phase IV open-label trial. PLoS One. 2013;8(2):e57222. doi: 10.1371/journal.pone.0057222. Epub 2013 Feb 28.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: October 22, 2008
• First Submitted That Met QC Criteria: October 22, 2008
• First Posted (Estimate): October 23, 2008

Study Record Updates

• Last Update Posted (Estimate): August 23, 2013
• Last Update Submitted That Met QC Criteria: August 19, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Body Weight; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: CV138-097