Glucagon-Like Peptide 1 Receptor Agonists for Obesity: Efficacy, Side Effects, and Risks

The glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) liraglutide and semaglutide, and the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RA tirzepatide are approved for the treatment of overweight and obesity. With increased utilization there have been concerns about potential risks. This review summarizes the current evidence on utilization of GLP-1 and dual GLP-1/GIP RAs in chronic weight management.

Newer generation GLP-1 based therapies have become more effective for the treatment of overweight and obesity, with data supporting tirzepatide as the most effective, followed by semaglutide and then liraglutide. Their clinical effects extend beyond weight loss, with evidence supporting their benefits on diabetes prevention, diabetes control, and improvement of cardiovascular disease and metabolic-associated steatotic liver disease (MASLD) outcomes. While side effects are common with this class of medications, most are mild-to-moderate and transient. Concerns have been raised about serious risks, including thyroid cancer, pancreatic disease, gastrointestinal paralysis, and suicidal ideation. However, data have yet to conclusively establish an association.

GLP-1 and dual GLP-1/GIP RAs are effective treatments for overweight, obesity, and adiposity-based chronic diseases. Like any intervention, their use should be based on risk-benefit analysis, taking into consideration individual patient factors.