03519nam a2200313   4500001000800000005001700008007000300025008004100028040000800069041000800077100003900085245006900124300002300193520250300216650003002719650001902749650002802768650002102796650004902817700003502866700003102901700002702932700002502959700003502984700002803019773011003047942003103157999001703188ESSALUD20260804150103.0ta      t        pe ||||| |||| 00| 0 spa d  aBMG  aeng  aMiller, Jennifer L. eAutor953703  aSetmelanotide for the treatment of acquired hypothalamic obesity  apáginas: 138-150  aBackground: A phase 2 trial of setmelanotide, a melanocortin-4 receptor agonist, showed substantial weight loss in patients with acquired hypothalamic obesity, but additional data are needed.
Methods: We conducted a phase 3 trial in which participants were randomly assigned in a 2:1 ratio to receive setmelanotide (at a dose of 1.5 to 3.0 mg) or placebo administered subcutaneously once daily for 52 weeks after a dose-escalation period. Persons at least 4 years of age were potentially eligible for the trial if they had acquired hypothalamic obesity, which was defined by a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) that was at or above the 95th percentile for age and sex (for participants <18 years of age) or at least 30 (for participants ≥18 years of age) and a history of a hypothalamic tumor, lesion, or injury. The primary end point was the mean percent change in BMI from baseline to 52 weeks after the end of the dose-escalation period. Secondary end points included the mean change in the weekly average of the maximal daily hunger score (range, 0 to 10, with higher scores indicating more severe hunger), assessed in participants at least 12 years of age. Results: From April 26, 2023, to March 18, 2025, a total of 120 participants were assigned to receive setmelanotide (81 participants) or placebo (39 participants). The mean (±SD) age was 19.9±13.8 years (range, 4 to 66). Among participants 18 years of age or older, the mean BMI was 41.2±9.7; the mean BMI z score among those younger than 18 years of age was 3.61±1.66. The least-squares mean (LSM) change in BMI at 52 weeks was −16.5% (95% confidence interval [CI], −19.3 to −13.8) with setmelanotide and 3.3% (95% CI, −0.6 to 7.2) with placebo (P<0.001), and the LSM change in the weekly average of maximal daily hunger scores was −2.73 (95% CI, −3.28 to −2.18) in the setmelanotide group and −1.45 (95% CI, −2.23 to −0.67) in the placebo group (P=0.009). Adverse events were reported in 100% of the participants in the setmelanotide group and in 90% of those in the placebo group, and serious adverse events were reported in 28% and 8%, respectively. The most common adverse events with setmelanotide were skin hyperpigmentation, nausea, vomiting, and headache.
Conclusions: Setmelanotide led to significantly greater reductions in BMI and hunger than placebo at 52 weeks among participants 4 to 66 years of age with acquired hypothalamic obesity.
  aMEDICINA CLÍNICA933681  aOBESIDAD91238  aENDOCRINOLOGÍA936891  aPEDIATRIA 96401  aENFERMEDAD HIPOTALÁMICO-HIPOFISARIA953704  aVan Santen, Hanneke M. 953705  aPhillips, Susan A. 953706  aHamilton, Jill 953707  aAberle, Jens 953708  aSathyapalan, Thozhukat 953709  aMohamed, Zainaba9537100 022717922635dMassachusetts NEJM GroupoNEJM002tThe New England Journal of Medicine wESSALUDx0028-4793  cARTICULOSe2026-07-30zsqb  c22731d22731