Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis
Bárbara Ferraz Barbosa, Francisco Cézar Aquino de Moraes, Camila Bordignon Barbosa, Plínio Takashi Karubi Palavicini Santos, Izael Pereira da Silva, Bruno Araujo Alves da Silva, Jamile Cristine Marques Barros, Rommel Mário Rodríguez Burbano, Ney Pereira Carneiro dos Santos, Marianne Rodrigues Fernandes
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; I2 = 92%), with an average proportion of −6.91% weight loss during treatment. Changes in BMI showed an MD of −10.55 kg/m2 in patients > 18 years and −0.61 kg/m2 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.