The effect of orlistat versus metformin on body composition and insulin resistance in obese premenopausal women: 3-month randomized prospective open-label study

Introduction: Our aim was to evaluate the effects of metformin and orlistat on body composition and glucose-insulin homeostasis in obese premenopausal women. Material and methods: Seventy-three obese premenopausal Caucasian women aged 32.4 +/- 8.3 years were treated with either metformin (1000 mg/day; n = 37) or orlistat (360 mg/day; n = 36). Anthropometric parameters were measured using dual-energy X-ray absorptiometry. Glucose tolerance, using the oral glucose tolerance test; insulin resistance, using the homeostasis model assessment (HOMA-IR); and insulin sensitivity, using the Matsuda insulin sensitivity index (ISI Matsuda), were assessed at the commencement of the study and after 3 months. Results: Those treated with orlistat showed greater weight loss (-9.4 +/- 2.3 vs. -4.9 +/- 1.3 kg, p < 0.05) and decrease of fat mass (-5.4 +/- 3.0 vs. -3.5 +/- 0.7 kg, p < 0.05) than those treated with metformin. The percentage of android and gynoid fat deposits was reduced in both groups; however, a greater decrease in android fat was observed in those treated with metformin. Improvement in ISI Matsuda and post-load insulin were similar in both groups. High initial post-load insulin and low ISI Matsuda corresponded with reductions in total fat, trunk fat, and waist circumference in both groups, and a decrease in android fat in those treated with metformin. Conclusions: Orlistat treatment resulted in greater weight loss and improvement in body composition; metformin treatment resulted in a reduction of android fat. Both drugs produced a comparable improvement in insulin/glucose homeostasis. Overall, insulin-resistant women showed improvement with treatment, irrespective of which drug was used.