Semaglutide Outperforms Other Drugs for Significant Weight Loss in Obesity

The global obesity epidemic continues to pose a significant public health challenge, driving increased rates of type 2 diabetes, cardiovascular disease, and certain cancers. While lifestyle interventions are foundational, many individuals require pharmacological support to achieve and maintain clinically meaningful weight loss. This systematic review addresses a critical knowledge gap by directly comparing the relative effectiveness of four commonly prescribed anti-obesity medications.

The analysis revealed significant differences in weight loss efficacy among the evaluated medications. Semaglutide consistently demonstrated superior weight reduction, with participants achieving an average 15.3% total body weight loss from baseline over 68 weeks. In comparison, liraglutide led to an average 8.5% weight loss, phentermine resulted in 6.2%, and orlistat showed the most modest effect at 4.1% total body weight reduction. Semaglutide provided a 1.8-fold greater weight loss than liraglutide, a 2.5-fold greater loss than phentermine, and a 3.7-fold greater loss than orlistat (all comparisons p<0.001). A higher proportion of individuals on semaglutide achieved >10% weight loss (69%) compared to liraglutide (38%), phentermine (25%), and orlistat (15%). Adverse events were generally mild to moderate, primarily gastrointestinal, with semaglutide and liraglutide showing similar tolerability profiles.