According to international guidelines, severe therapy-resistant obesity can be treated with anti-obesity medicine as add-on therapy to a healthy lifestyle or bariatric surgery. Metformin is known for its subtle weight reducing potential, but not yet approved as pharmacotherapeutic agent for obesity. Recent animal studies suggest beneficial effects on defective leptin-melanocortin signaling in the hypothalamus. Therefore, we hypothesized that metformin could have beneficial effects on weight and hyperphagia in patients with severe therapy-resistant obesity, which may be related to disturbed leptin-melanocortin signaling.

This case report describes the effect of high dosed metformin (3x1000mg) in an adult patient with severe early-onset obesity, hyperphagia, and a heterozygous POMC gene variant of uncertain significance. Within 4 months, he accomplished a weight reduction of -10,6 kg (-6,5%), facilitated by an improved satiety. In the subsequent 1,5 years, after addition of liraglutide 3.0mg, he lost an additional -4.6 kg of weight, adding up to a sustained -9.1% weight loss, BMI decrease of -4.2kg/m² and improved glycemic control over 20 months’ time.

This case offers arguments to test the effect of this inexpensive and safe drug as a first pharmacological step in the treatment of patients with severe obesity and a clinical phenotype suggestive of genetic obesity.