Metformin for overweight women at midlife: a double-blind, randomized, controlled trial

Abstract

Aim This study was undertaken to determine whether metformin would ameliorate insulin resistance, reduce weight and waist circumference and improve lipids in obese, but not morbidly obese, euglycemic women.

Methods Obese women (body mass index (BMI) ≥ 30 and < 40 kg/m² and/or waist circumference > 88 cm), aged 35–65 were randomized (1:1) to metformin 850 mg or identical placebo, twice daily for 26 weeks. The primary outcome was the change in insulin resistance determined by the homeostasis model of assessment (HOMA-IR). Secondary outcomes included fasting insulin, glucose, weight, waist circumference and BMI.

Results Of the 125 women screened, 117 enrolled and 100 women, mean age 53 years, were included in the primary intention-to-treat analysis. Metformin resulted in statistically significant between-group difference in the change in HOMA-IR (change in median − 0.04 vs. placebo + 0.1, p = 0.018) and BMI (mean change − 1.00 kg/m²; 95% confidence interval (CI) 1.37 to − 0.62 vs. placebo mean change 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 decrease in high density lipoprotein cholesterol (p = 0.07) were also observed for metformin, compared with placebo. No effects were seen for waist circumference, fasting glucose or other lipids.

Conclusion Treatment of euglycemic, obese, middle-aged women with metformin 1700 mg per day reduced insulin resistance and weight compared with placebo. Further studies are needed to determine whether the use of metformin will prevent the progression of insulin resistance to type 2 diabetes mellitus in obese women.

Key words::

• INSULIN RESISTANCE
• OBESITY
• METFORMIN
• WOMEN

Conflict of interest S.R.D. is a consultant and investigator for Trimel Pharmaceuticals and has research grant support from Lawley Pharmaceuticals and Besins Health Care. The authors alone are responsible for the content and writing of the paper.

Source of funding This study was supported by the Bupa Health Foundation, Australia. Ascent Pty Ltd supplied the metformin and placebo but played no role in the study design, data collection, analyses or writing of this publication. R.W. has a NHMRC postgraduate scholarship. S.R.D. is an NHMRC principal research fellow (grant number 1041853).