This review explores the molecular mechanisms and therapeutic potential of semaglutide and liraglutide, two glucagon-like peptide-1 receptor agonists (GLP-1RAs), in the treatment of obesity. Obesity, a chronic disease with increasing prevalence, is associated with various health risks, including cardiovascular diseases, type 2 diabetes, hypertension, and cancer. GLP-1RAs, originally developed for treating type 2 diabetes, have shown significant weight loss and metabolic benefits in obese individuals. The review highlights the activation of the GLP-1 receptor (GLP-1R) by semaglutide and liraglutide, which triggers several metabolic pathways. These pathways include the cAMP/PKA signaling cascade, which enhances insulin secretion and suppresses glucagon release, and the AMPK pathway, which regulates glucose homeostasis and lipid metabolism. The drugs also modulate appetite and energy expenditure through the activation of the Wnt/β-catenin signaling pathway and the sympathetic nervous system. Clinical trials have demonstrated the effectiveness of semaglutide and liraglutide in reducing body weight and improving metabolic parameters. Semaglutide, in particular, has shown superior outcomes, with a higher weight loss rate and a lower incidence of side effects compared to liraglutide. The review also discusses the potential of these drugs in treating other obesity-related conditions, such as cardiovascular diseases, fatty liver disease, and neurodegenerative disorders. In conclusion, semaglutide and liraglutide represent promising therapeutic options for obesity, offering significant weight loss and metabolic benefits. Further research is needed to optimize their use and explore additional therapeutic applications.This review explores the molecular mechanisms and therapeutic potential of semaglutide and liraglutide, two glucagon-like peptide-1 receptor agonists (GLP-1RAs), in the treatment of obesity. Obesity, a chronic disease with increasing prevalence, is associated with various health risks, including cardiovascular diseases, type 2 diabetes, hypertension, and cancer. GLP-1RAs, originally developed for treating type 2 diabetes, have shown significant weight loss and metabolic benefits in obese individuals. The review highlights the activation of the GLP-1 receptor (GLP-1R) by semaglutide and liraglutide, which triggers several metabolic pathways. These pathways include the cAMP/PKA signaling cascade, which enhances insulin secretion and suppresses glucagon release, and the AMPK pathway, which regulates glucose homeostasis and lipid metabolism. The drugs also modulate appetite and energy expenditure through the activation of the Wnt/β-catenin signaling pathway and the sympathetic nervous system. Clinical trials have demonstrated the effectiveness of semaglutide and liraglutide in reducing body weight and improving metabolic parameters. Semaglutide, in particular, has shown superior outcomes, with a higher weight loss rate and a lower incidence of side effects compared to liraglutide. The review also discusses the potential of these drugs in treating other obesity-related conditions, such as cardiovascular diseases, fatty liver disease, and neurodegenerative disorders. In conclusion, semaglutide and liraglutide represent promising therapeutic options for obesity, offering significant weight loss and metabolic benefits. Further research is needed to optimize their use and explore additional therapeutic applications.