Setmelanotide

Setmelanotide (Imcivree) is an FDA-approved MC4R agonist for chronic weight management in patients with obesity due to specific genetic conditions (POMC, PCSK1, or LEPR deficiency).

Mechanism of Action

Selective agonist of melanocortin 4 receptors (MC4R) in the hypothalamus, restoring the satiety signaling pathway that is disrupted in certain genetic obesity syndromes.

Typical Dosage (Research)

Adults: Start 2mg daily, titrate based on tolerability up to 3mg daily. Pediatrics (6+): Weight-based dosing starting at 1mg daily.

Subcutaneous injection once daily. Requires genetic testing to confirm eligible mutations before prescribing.

Side Effects & Risks

Injection site reactions, skin hyperpigmentation, spontaneous penile erections, depression, and suicidal ideation (boxed warning). GI effects less common than GLP-1s.

Boxed warning for depression and suicidal ideation - requires monitoring. May cause sexual adverse reactions. Only for genetically confirmed obesity.

Who Uses Setmelanotide

Patients with genetically confirmed POMC, PCSK1, or LEPR deficiency obesity - a very specific population.