Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Apr 1;30(2):136-140.
doi: 10.1097/MED.0000000000000798. Epub 2023 Feb 1.

Setmelanotide: a promising advancement for pediatric patients with rare forms of genetic obesity

Christine M Trapp  1   2 , Marisa Censani  3
Affiliations
Review

Setmelanotide: a promising advancement for pediatric patients with rare forms of genetic obesity

Christine M Trapp et al. Curr Opin Endocrinol Diabetes Obes. .

Abstract

Purpose of review: Examine Setmelanotide use in patients with rare genetic variants that disrupt the melanocortin pathway.

Recent findings: Between February 2017 and September 2018, 10 participants with pro-opiomelanocortin (POMC)/ proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency and 11 participants with leptin receptor (LEPR) deficiency were enrolled in open-label, phase 3 trials at 10 centers in the United States and internationally to assess the efficacy and safety of the melanocortin-4 receptor (MC4R) agonist Setmelanotide. 80% of POMC participants and 45% of LEPR participants achieved at least 10% weight loss at 1 year. Significant changes in hunger scores were seen for both cohorts as well. Setmelanotide was well tolerated with injection site reactions and hyperpigmentation being the most common adverse events reported. As a result, Setmelanotide was approved by the U.S. FDA in 2020 for chronic weight management in adult and pediatric patients ≥6 years of age with POMC, LEPR, or PCSK1 deficiency. In 2022, its approval was extended to include patients with Bardet-Biedel syndrome (BBS) after phase 3 trial data showed that, on average, Setmelanotide treatment resulted in a BMI loss of 7.9% for the 44 BBS participants.

Summary: Rare genetic variants such as POMC, LEPR, and PCSK1 deficiency disrupt MC4R pathway signaling, resulting in severe early-onset obesity, hyperphagia, and increased risk for metabolic co-morbidities. Patients with BBS also demonstrate severe early-onset obesity and hyperphagia, due in part to defective MC4R signaling. Setmelanotide has shown promising benefits in improving satiety scores and weight-related outcomes in patients with these early-life genetic obesity conditions, although longer-term studies are needed.

Trial registration: ClinicalTrials.gov NCT04963231.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest.

Figures

Box 1
Box 1
no caption available
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Organization WH. Fact sheets: obesity and overweight. 2020. Available at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
    1. Hu K, Staiano AE. Trends in obesity prevalence among children and adolescents aged 2 to 19 years in the US from 2011 to 2020. JAMA Pediatr 2022; 176:1037–1039. - PMC - PubMed
    1. Ranadive SA, Vaisse C. Lessons from extreme human obesity: monogenic disorders. Endocrinol Metab Clin North Am 2008; 37:733–751. x. - PMC - PubMed
    1. Huvenne H, Dubern B, Clement K, Poitou C. Rare genetic forms of obesity: clinical approach and current treatments in 2016. Obes Facts 2016; 9:158–173. - PMC - PubMed
    1. Yazdi FT, Clee SM, Meyre D. Obesity genetics in mouse and human: back and forth, and back again. PeerJ 2015; 3:e856. - PMC - PubMed

Supplementary concepts

Associated data