Long-Term MC4R Agonist Treatment in POMC-Deficient Patients

This correspondence reports long-term outcomes (7.2 and 6.8 years) of MC4R agonist (setmelanotide) treatment in two adult patients with proopiomelanocortin (POMC) deficiency, a rare cause of severe early-onset obesity due to impaired melanocortin signaling. Key findings include:

• Weight reduction: Sustained decreases of 35.8% (−55.6 kg) and 47.5% (−72.6 kg) in body weight, with BMI standard-deviation scores improving from 4.5 to 2.7 and 4.8 to 2.1, respectively.

• Metabolic benefits: Normalization of hyperinsulinemia and hunger scores (Likert scale: pre-study scores of 9–10 reduced to 2–5).

• Safety: No persistent adverse effects beyond skin/hair pigmentation changes.
  The study highlights the efficacy of targeted therapy for monogenic obesity and underscores the importance of genetic diagnosis in severe obesity cases.

This correspondence reports long-term outcomes (7.2 and 6.8 years) of MC4R agonist (setmelanotide) treatment in two adult patients with proopiomelanocortin (POMC) deficiency, a rare cause of severe early-onset obesity due to impaired melanocortin signaling. Key findings include:

• Weight reduction: Sustained decreases of 35.8% (−55.6 kg) and 47.5% (−72.6 kg) in body weight, with BMI standard-deviation scores improving from 4.5 to 2.7 and 4.8 to 2.1, respectively.

• Metabolic benefits: Normalization of hyperinsulinemia and hunger scores (Likert scale: pre-study scores of 9–10 reduced to 2–5).

• Safety: No persistent adverse effects beyond skin/hair pigmentation changes.
  The study highlights the efficacy of targeted therapy for monogenic obesity and underscores the importance of genetic diagnosis in severe obesity cases.