Additionally, GLP-1 analogs reduced energy expenditure, with only tirzepatide showing a significant decrease in the respiratory quotient (RQ) in MC4R KO mice.<h4>Conclusion</h4>Our findings demonstrate that all three GLP-1 analogs, semaglutide, tirzepatide, and retatrutide, exhibit significant anti-obesity effects in MC4R KO mice. Here, GCG is linked to obesity due to melanocortin 4 receptor deficiency.