Metformin and Topiramate for Weight Loss

FDA-Approved Weight Loss Medications vs. Off-Label Options

The FDA-approved phentermine and topiramate extended-release (Qsymia) is used for weight loss, with significant weight loss of 7.8% and 9.8% at 7.5/46 mg and 15/92 mg doses respectively, compared to 1.2% with placebo 3
Phentermine/topiramate ER is available in 4 doses: 3.75/23 mg, 7.5/46 mg, 11.25/69 mg, and 15/92 mg, and demonstrated long-term efficacy in the SEQUEL trial with persistent weight loss at 108 weeks (9.3% and 10.5% at 7.5/46 mg and 15/92 mg doses) 1, 2, 3

The American Gastroenterological Association recommends starting phentermine/topiramate ER with 3.75/23 mg daily for 14 days, then increasing to 7.5/46 mg daily, with a maximum dose of 15/92 mg daily 4, 5
Discontinuation is recommended if less than 5% weight loss is achieved after 12 weeks at the maximum dose 4, 5

Topiramate carries a risk of orofacial clefts in infants exposed during the first trimester of pregnancy, and may reduce the efficacy of hormonal contraceptives 3, 5
Common side effects of topiramate include paresthesias, dizziness, dysgeusia, insomnia, constipation, and dry mouth 3, 5

For patients requiring significant weight loss with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities, the American College of Gastroenterology recommends FDA-approved medications like phentermine/topiramate ER as first-line 4, 7
The American Diabetes Association suggests considering off-label metformin and topiramate combination in patients with comorbid conditions that might benefit from these medications (diabetes for metformin, migraines for topiramate) 4

Regular monitoring of blood pressure and heart rate is recommended, as well as assessment of efficacy and safety at least monthly for the first 3 months, then every 3 months 4, 7
Pregnancy tests are recommended for women of childbearing potential 4, 5