Moreover, an MC4R agonist, setmelanotide (Set), which has a 20-fold MC4R selectivity compared with α-MSH (51), has been effective for weight loss in patients with the MC4R/POMC/leptin pathway polymorphism and has been approved by the FDA for treatment of obesity in these patients (50, 52–54). Here, POMC is linked to obesity due to melanocortin 4 receptor deficiency.