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Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison

Kosuke Hitaka, Takumi Sugawara, Mitsuharu Matsumoto +1 more2026International Journal of Obesity
10.1038/s41366-026-02025-2
Endocrine (ADH/ACTH/MSH)

Abstract

Our findings demonstrate that all three GLP-1 analogs, semaglutide, tirzepatide, and retatrutide, exhibit significant anti-obesity effects in MC4R KO mice. These results suggest that GLP-1 analogs may provide an effective treatment option for patients with MC4R-POMC pathway deficiencies. Moreover, the efficacy of these drugs in MC4R KO mice aligns with clinical studies, indicating that MC4R KO mice serve as a reliable animal model for obesity research.

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