In Phase 3 clinical trials, the melanocortin-4 receptor agonist setmelanotide significantly reduced weight and hunger in patients with obesity due to POMC or LEPR deficiency, as reported by Clément et al. [20] Patients in the POMC and LEPR trials experienced mean (standard deviation [SD]) weight loss of 25.6% (9.9%; P < 0.0001) and 12.5% (8.9%; P < 0.0001), respectively, and mean (SD) hunger reduction of 27.1% (28.1%; P = 0.0005) and 43.7% (23.7%; P < 0.0001), respectively, after ~ 52 weeks of setmelanotide [23]. Here, LEPR is linked to obesity due to melanocortin 4 receptor deficiency.