Abstract
BACKGROUND: A malfunction in the melanocortin-4 receptor (MC4R) is associated with obesity in rare genetic syndromes; setmelanotide is a new drug that activates this receptor and is being used to treat severe obesity. This meta-analysis evaluated the efficacy and safety of setmelanotide for weight loss in severe obesity linked to human MC4R deficiency. METHODS: We searched PubMed, Embase, and Cochrane for randomized and nonrandomized clinical trials using setmelanotide. We considered a p-value ≤ 0.05 statistically significant. RESULTS: We included 376 patients, of whom 328 (87.2%) received setmelanotide for a mean follow-up of 52 weeks. The mean age was 32.8 (14.67) years. Weight loss was significant (MD -3.52; 95% CI -3.98, -3.05; p = 0.01; I(2) = 92%), with an average proportion of -6.91% weight loss during treatment. Changes in BMI showed an MD of -10.55 kg/m(2) in patients > 18 years and -0.61 kg/m(2) in patients < 18 years (BMI score). However, the drug was associated with a higher risk of skin hyperpigmentation (OR 0.69; 95% CI 0.55, 0.80; p = 0.08). CONCLUSIONS: Our results support the use of setmelanotide in treating severe obesity.