Setmelanotide for the Treatment of Acquired Hypothalamic Obesity

New England Journal of Medicine 2026 Open access

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Authors: Jennifer L. Miller, H. M. van Santen, Susan A. Phillips, Jill Hamilton, Jens Aberle, Thozhukat Sathyapalan, Zainaba Mohamed, Shana E. McCormack, Ashley H. Shoemaker, Megan M. Kelsey, Luma Ghalib, Guenter Stalla
+21 more Vidhu Thaker, Reema Habiby, KATIE LARSON ODE, Martin Wabitsch, MT Dattani, M. Jennifer Abuzzahab, Hussein Abdullatif, Ryan Morgan, Margaret Stefater-Richards, Vanita R. Aroda, Carsten Friedrich, Joan C. Han, Hiraku Ono, Keisuke Nagasaki, Tomohiro Tanaka, Tsuyoshi Isojima, Hiroshi Arima, Cecilia Scimia, Guojun Yuan, Hermann L. Müller, Christian L. Roth
DOI: 10.1056/nejmoa2512275
Cited by: 7
References: 40

Abstract

BACKGROUND: 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

Fields of Study & Subjects

Regulation of Appetite and Obesity Pharmacology and Obesity Treatment Pituitary Gland Disorders and Treatments

Publication details

Journal / source
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Volume
395
Issue
2
Pages
138–150
Publication date
8 July 2026
Language
EN