We studied people with obesity involved in the SURMOUNT-1 trial of the dual GLP-1 and GIP receptor agonist, tirzepatide. People with pathogenic variants of the gene encoding the melanocortin 4 receptor (MC4R) lost a similar amount of weight to people with an intact gene, demonstrating that tirzepatide is effective in MC4R deficiency.
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References
van der Klaauw, A. A. & Farooqi, I. S. The hunger genes: pathways to obesity. Cell. 161, 119–132 (2015). A review that presents evidence for the genetic and environmental contribution to obesity.
Farooqi, I. S. et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 348, 1085–1095 (2003). This paper reports the frequency of pathogenic MC4R mutations in children with severe obesity and the associated clinical phenotype.
Reinehr, T. et al. Lifestyle intervention in obese children with variations in the melanocortin 4 receptor gene. Obesity 17, 382–389 (2009). This paper reports that dietary restriction is less effective in reducing body weight in children with obesity due to MC4R deficiency compared with children with common obesity.
Jastreboff, A. M. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 387, 205–216 (2022). This paper reports results of the SURMOUNT-1 trial of the dual GLP-1 and GIP receptor agonist, tirzepatide, which showed significant weight loss in adults with common obesity.
Clemmensen, C. et al. Dual melanocortin-4 receptor and GLP-1 receptor agonism amplifies metabolic benefits in diet-induced obese mice. EMBO Mol. Med. 7, 288–298 (2015). This paper reports that diet‐induced obese mice chronically treated with the GLP‐1 receptor agonist liraglutide and the MC4R agonist RM‐493 lose more weight than diet‐induced obese mice treated with either drug on its own.
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This is a summary of: Bhatnagar, P. et al. Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency. Nat. Med. https://doi.org/10.1038/s41591-025-03913-2 (2025).
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Tirzepatide drives weight loss in people with obesity due to MC4R deficiency. Nat Med 31, 3260–3261 (2025). https://doi.org/10.1038/s41591-025-03915-0
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DOI: https://doi.org/10.1038/s41591-025-03915-0