Aim: Evidence to support the use of metformin to treat insulin resistance (IR) and prevent progression to type 2 diabetes mellitus (T2DM) in its preclinical phase is lacking. The aim of this study was to determine whether metformin would reduce IR, weight and waist circumference and improve lipids and lower sex hormone binding globulin (SHBG) in obese, but not morbidly obese, euglycaemic women.
Methods: Obese women (body mass index (BMI) >30 and < 40 kg/m2 and/or waist circumference >88cm), aged 35-65 were randomised (1:1) to metformin 850mg, or identical placebo, twice daily for 26 weeks. The primary study outcome was the change in IR determined by the homeostasis model of assessment (HOMA-IR). Secondary outcomes included fasting insulin, glucose, weight, waist circumference and BMI. The trial was registered on ACTRN12610000836033.
Results: 125 women were screened, 117 enrolled and 100 women, mean age 53 years, were included in the primary intention to treat analysis. Metformin treatment resulted in statistically significant between group difference in the change in HOMA-IR (mean change -0.38; 95% CI of mean -0.54 to -0.22, vs placebo -0.13; 95% CI -0.50 to 0.24, p=0.018) and BMI (mean change -1.00 kg/m2; 95% CI of mean -1.37 to -0.62 vs placebo 0.00; 95% CI -0.29 to 0.28, p<0.001). Statistically significant reductions in HbA1C (p=0.008) and fasting insulin (p=0.03) and a borderline increase in HDL-C (p=0.07) were also observed for metformin, compared with placebo. No effects were seen for waist circumference, fasting glucose, other lipids or SHBG.
0>Conclusion: Treatment of euglycemic obese middle-aged women with metformin 1700 mg/ day resulted in improved IR and weight loss compared with placebo. Our findings support the use of metformin in obese, but not morbidly obese, middle-aged women.
This study was supported by the Bupa Health Foundation, Australia.