Recently, glucagon-like peptide-1 (GLP-1) analogs, including semaglutide, tirzepatide, and retatrutide, have been explored as potential anti-obesity therapies.<h4>Methods</h4>This study aimed to assess and compare the efficacy of these GLP-1 analogs in MC4R knockout (KO) mice, which are deficient in the POMC-MC4R pathway. This evidence concerns the gene GCG and obesity due to melanocortin 4 receptor deficiency.