Summary: In women with PCOS and obesity or overweight plus cardiometabolic risk, adding low-dose topiramate to metformin improved 6-month weight loss versus placebo (-4.5% vs -1.4%; between-group P=.03). The benefit was modest, paresthesia was more common, and the study was too small and short to settle longer-term reproductive or metabolic outcomes.
PICO Summary
| Element | Detail |
|---|---|
| Population | 61 women aged 14-40 years with PCOS and obesity (BMI ≥30 kg/m2) or BMI ≥27 kg/m2 plus hypertension, type 2 diabetes, or dyslipidemia; double-blind, placebo-controlled RCT over 6 months. |
| Intervention | Topiramate added to metformin plus a 20-kcal/kg diet and desogestrel contraception: 25 mg nightly for 15 days, then 50 mg nightly, doubled at 3 months if weight loss remained <3% (n=30). |
| Comparison | Matching placebo added to metformin, the same diet, and the same contraception strategy, with the same dose-escalation rule (n=31). |
| Outcome | Mean body-weight change at 6 months was -4.5% with topiramate versus -1.4% with placebo (between-group P=.03). At 3 months it was -3.4% versus -1.6% (P=.03); paresthesia occurred in 23.3% versus 3.2% (P=.026). |
Topiramate Added to Metformin for Obesity Control in...
Primary RCT · Obesity & weight management
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.
Expert Commentary
This small but well-conducted double-blind trial asks a practical question that comes up often in PCOS clinics: can low-dose topiramate add meaningful weight benefit to metformin and diet? The answer is yes, but the gain is modest. A 3.1-point greater percentage weight reduction at 6 months is clinically relevant for some patients, especially when even modest weight loss can improve metabolic and reproductive risk in PCOS. The signal is strengthened by the randomized design, good pill adherence, and a concordant waist-circumference benefit. Can I use this with my patients? Selectively, and usually only in specialist practice after counseling. The study enrolled just 61 participants, follow-up lasted 6 months, and there was no active obesity-drug comparator, so this is not the same as proving superiority over modern anti-obesity pharmacotherapy. The adverse-effect pattern also matters: paresthesia was clearly more frequent, and topiramate raises practical concerns around cognition, mood, and pregnancy prevention even when used at relatively low dose. I would view this as an off-label option for women with PCOS and obesity who are already taking metformin, cannot access or tolerate preferred obesity therapies, and can adhere to contraception and follow-up. It should change conversations more than it changes first-line prescribing.
References
Marchesan LB, da Silva TR, Spritzer PM. Topiramate added to metformin for obesity control in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2025;110(6):e1892-e1901. doi:10.1210/clinem/dgae637. PMID: 39271474.