A paper by researcher Hitaka of the Pharmacology Business Unit has been published in the International Journal of Obesity.

2026.02.25

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

Publication
Published Date: 21 February 2026
Authors: Kosuke Hitaka, Takumi Sugawara, Mitsuharu Matsumoto, and Yasunori Nio

In the evaluation of anti-obesity drugs, diet-induced obesity (DIO) mouse models are commonly used; however, these models require more than six months to develop a stable obese phenotype, resulting in a prolonged timeline for pharmacological evaluation. In contrast, melanocortin-4 receptor (MC4R)–deficient mice develop severe obesity at an earlier age than DIO mice and therefore represent a useful model for the rapid assessment of anti-obesity agents. In this study, we evaluated the anti-obesity effects of multiple GLP-1 analogs in MC4R-deficient mice to examine the translational relevance of this model to human obesity. As a result, the magnitude and pattern of body-weight reduction observed in this model were highly consistent with clinical outcomes reported in humans. In addition, a reduction in lean body mass—an adverse effect reported as a clinical risk associated with GLP-1 analog therapy—was also observed, further supporting the high translational validity of this model.　 Furthermore, our finding suggest that MC4R-deficient mice are a useful preclinical model even when considering obesity pathophysiology associated with impaired MC4R signaling, such as Prader–Willi syndrome.
We anticipate that the results of this study will contribute to the advancement of drug discovery research in the field of obesity.

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