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NB improves central obesity and LDL levels but without significant improvement in other cardiovascular parameters.61,62,73,125 NB is effective in binge eating disorder, which presents a patient population potentially best served by this medication.126 Setmelanotide Setmelanotide is a daily subcutaneous injection which acts as a melanocortin-4 (MC4) receptor agonist, and was approved by the FDA in 2020 in patients with obesity arising from genetically confirmed Bardet-Biedl syndrome (BBS), POMC, PCSK1, or LEPR deficiency.127,128 Human studies of setmelanotide showed significant weight loss and improved hunger scores.129 A phase 2 study of 18 patients with hypothalamic obesity found that setmelanotide led to 80% experiencing 5% body weight loss at 16 weeks.130 Adverse events of setmelanotide include nausea, depression, suicidal ideation, and hyperpigmentation.127,129131 Its use remains limited for these genetic alterations in MC4R signaling and given its specific actions is unlikely to be effective in the general population