Study compares semaglutide, tirzepatide, and retatrutide in a genetic obesity mouse model
A peer-reviewed study in the International Journal of Obesity compares three GLP-1–class peptides — semaglutide, tirzepatide, and retatrutide — in a genetic mouse model of obesity.
The researchers used MC4R-knockout mice, which lack a receptor central to the brain’s appetite-regulating melanocortin pathway and develop obesity, insulin resistance, and markers of liver stress. Over a 21-day dosing period, all three peptides produced significant reductions in body weight in the model — reported as roughly 20% for semaglutide, about 32% for tirzepatide, and about 24% for retatrutide — alongside improvements in measures such as plasma insulin and liver-injury markers. The authors note the relative ordering broadly tracks what has been seen in human studies, which they argue supports the model’s usefulness for obesity research.
This is preclinical animal research, not a human trial, and the percentages refer to mice rather than people; the work is most useful as mechanistic and comparative context for a peptide class that dominates current regulatory and research discussion. We summarize it as science news only and do not interpret it as treatment guidance.
Primary source (peer-reviewed): International Journal of Obesity (2026): “Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison”
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For informational and educational use only — not medical advice. Intended for adults 21+.