Topiramate added to metformin for obesity control in women with polycystic ovary syndrome: a randomized clinical trial

Abstract Context Polycystic ovary syndrome (PCOS) is often linked with obesity, and weight management can improve endocrine and cardiometabolic features. Objective To evaluate the effects of adding topiramate (TPM) to metformin (MTF) on weight control, hormonal and metabolic outcomes in women with PCOS. Methods In a randomized, double-blind, placebo-controlled trial, participants with PCOS and body mass index ≥30 kg/m² or ≥27 kg/m² associated with hypertension, type 2 diabetes, or dyslipidemia followed a 20 kcal/kg diet in addition to 850 mg of MTF or a previous MTF regimen. They were randomized to receive either TPM or placebo (P) alongside MTF. Anthropometric measurements, blood pressure, modified Ferriman-Gallwey score (mFGS), and adverse events were assessed every 4 weeks for 6 months. Main Outcome Measures The primary endpoint was the percent change in body weight from baseline in both groups. Secondary endpoints included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features. Results Thirty-one participants were in the MTF+P group and 30 in the MTF+TPM group. The MTF+TPM group showed greater mean weight loss at 3 months (-3.4% vs. -1.6%, p=0.03) and 6 months (-4.5% vs. -1.4%, p=0.03). Both groups improved androgens, lipids, and psychosocial scores. Participants with ≥3% weight loss at 6 months improved mFGS (8.4 to 6.5, p=0.026). Paresthesia was more common in the MTF+TPM group (23.3% vs. 3.2%, p=0.026). Conclusions Combining TPM with MTF and a low-calorie diet may be an effective, low-cost, easy-to-use, and safe strategy for weight management in women with PCOS, with mild adverse effects.