Comparing Drug Efficacy for Weight Loss in Adults Without Diabetes

The global prevalence of overweight and obesity continues to rise, posing significant public health challenges due to associated comorbidities like cardiovascular disease, metabolic syndrome, and certain cancers. While lifestyle interventions are foundational, many individuals struggle to achieve and maintain clinically meaningful weight loss with diet and exercise alone. This systematic review and meta-analysis addresses the critical need for a comprehensive, comparative evaluation of pharmacological treatments specifically for adults with overweight or obesity who do not have type 2 diabetes, providing clarity on their efficacy and safety profiles.

The meta-analysis revealed significant and varied weight loss efficacy across different drug classes. GLP-1 receptor agonists demonstrated the most substantial reductions in body weight. For instance, semaglutide (at 2.4 mg weekly) led to an average 14.9% (95% CI: 13.8% to 16.0%) reduction in body weight compared to placebo, while tirzepatide (at 15 mg weekly) showed an even greater average reduction of 20.9% (95% CI: 19.5% to 22.3%). Other effective treatments included liraglutide (3.0 mg daily), resulting in a 6.4% weight loss, and phentermine/topiramate, which achieved a 9.3% reduction. The most impactful finding was that tirzepatide consistently delivered the highest mean percentage body weight reduction, with 75% of participants achieving at least 5% weight loss, and 43% achieving 15% or more, significantly outperforming other agents (p<0.001). Adverse events, primarily gastrointestinal (nausea, diarrhea), were common but generally mild to moderate, with discontinuation rates due to adverse events ranging from 5% to 15% across the different drug groups, slightly higher than placebo (p<0.05 for most active treatments).