Setmelanotide

Setmelanotide is an FDA- and EMA-approved MC4R (melanocortin 4 receptor) agonist used for the treatment of genetic obesity syndromes such as POMC, LEPR, or PCSK1 deficiency. It acts centrally to restore appetite regulation and reduce hyperphagia, leading to significant weight loss in responsive populations. It is considered one of the first targeted obesity treatments based on melanocortin biology and is being explored for broader metabolic use.

• Melanocortin 4 receptor agonist

• unit: mg

  low dose: 1

  frequency: Once daily

  high dose: 3

  standard dose: 2

  administration route: Subcutaneous (SQ)

• Administered once daily. Initiate at 1 mg and titrate to 2–3 mg based on response. Long-term or continuous use is permitted with regular monitoring of BMI, leptin response, appetite suppression, and metabolic labs. Typically not cycled unless due to tolerability issues or therapeutic plateau.

common: ["Nausea","Vomiting"]

warnings: ["Severe allergic reactions"]

long term: ["Potential unknown long-term effects"]

sequence: H-Asp-Lys-Val-Met-Asp-Glu-D-Phe-D-Trp-Lys-(gamma-turn)-Gln-His-Edge-NH2

half life: 12 hours

degradation: Setmelanotide is metabolized and excreted primarily via the kidneys.

molecular weight: 1020.18

molecular formula: C49H69N15O7

tissue specificity: It targets pathways involved in regulating hunger and energy expenditure.

• Efficacy and safety of setmelanotide in severe obesity due to LEPR or POMC deficiency: phase 3.clinicalPMID 33137293 ↗
• Setmelanotide in patients aged 2-5 years with MC4R pathway-associated obesity (VENTURE).clinicalPMID 39549719 ↗