Impact of baseline BMI on glycemic control and weight change with metformin monotherapy in Chinese type 2 diabetes patients: phase IV open-label trial

Abstract

Background: Differences exist between treatment recommendations regarding the choice of metformin as first-line therapy for type 2 diabetes patients according to body mass index (BMI). This study compared the efficacy of metformin monotherapy among normal-weight, overweight, and obese patients with newly diagnosed type 2 diabetes.

Methods: In this prospective, multicenter, open-label study in China, patients aged 23-77 years were enrolled 1∶1:1 according to baseline BMI: normal-weight (BMI 18.5-23.9 kg/m(2); n = 125); overweight (BMI 24.0-27.9 kg/m(2); n = 122) or obese (BMI ≥28 kg/m(2); n = 124). Extended-release metformin was administered for 16 weeks (500 mg/day, up-titrated weekly to a maximum 2,000 mg/day). The primary efficacy endpoint was the effect of baseline BMI on glycemic control with metformin monotherapy, measured as the change from baseline in glycosylated hemoglobin (HbA1c) at week 16 compared among BMI groups using ANCOVA. Other endpoints included comparisons of metformin's effects on fasting plasma glucose (FPG), lipid levels and body weight.

Results: Mean HbA1c decreases at week 16, adjusted for baseline values, were -1.84%, -1.78% and -1.78% in normal-weight, overweight and obese patients, (P = 0.664); body weight decreased by 2.4%, 3.9% and 3.5%, respectively. FPG levels decreased similarly over time in all BMI groups (P = 0.461) and changes from baseline in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) did not differ significantly among BMI groups at week 16 (P = 0.143 and 0.451, respectively).

Conclusions: Baseline BMI had no impact on glycemic control, weight change or other efficacy measures with metformin monotherapy. These data suggest that normal-weight type 2 diabetes patients would derive the same benefits from first-line treatment with metformin as overweight and obese patients, and are not at increased risk of excess weight loss.

Trial registration: ClinicalTrials.gov NCT00778622.

Conflict of interest statement

Competing Interests: The authors LJ, XG and RH have received honoraria for attending Advisory Board meetings for Bristol-Myers Squibb and have received payment for lectures. LJ and XG are investigators in clinical trials of other compounds under development by Bristol-Myers Squibb. ZZ is an employee of Bristol-Myers Squibb and has received stock/stock options from Bristol-Myers Squibb. This study was funded by Bristol-Myers Squibb. Statistical analyses were performed by MJ and XK of Pharmaceutical Product Development, Inc., paid for by Bristol-Myers Squibb. Editorial assistance with preparation of the manuscript was provided by Samantha Santangelo, PhD, of MediTech Media Asia Pacific Pte Ltd, paid for by Bristol-Myers Squibb. HL is an employee of Sino-American Shanghai Squibb Pharmaceutical Ltd. Metformin which was used in this study is a product of Bristol-Myers Squibb. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. CONSORT flow diagram of patient disposition.

BMI, body mass index.

Figure 2. Changes over time according to baseline BMI in the full analysis set population.

(A) Mean fasting plasma glucose (FPG) levels; (B) Mean body weight. Error bars represent standard deviation (SD).