Safety and effects of anti-obesity medications on weight loss, cardiometabolic, and psychological outcomes in people living with overweight or obesity: a systematic review and meta-analysis.

Summary

Synthesizing 154 RCTs (n=112,515), this meta-analysis ranks anti-obesity medications: tirzepatide delivers the greatest weight loss and strong blood pressure/glucose reductions; semaglutide and liraglutide lower major adverse cardiovascular events. Naltrexone/bupropion may raise blood pressure, and phentermine/topiramate carries higher psychological adverse event risk.

Key Findings

• Among 154 RCTs (n=112,515), tirzepatide showed the greatest weight-loss effect (WMD -11.69 kg; 95% CI -19.22 to -4.15).
• Tirzepatide provided the strongest blood pressure and glucose-lowering benefits among agents evaluated.
• Semaglutide and liraglutide reduced major adverse cardiovascular events (MACEs).
• Naltrexone/bupropion was associated with increased blood pressure risk.
• Phentermine/topiramate had a higher risk of psychological adverse effects.

Clinical Implications

Prioritize tirzepatide for maximal weight loss and broad cardiometabolic benefit; consider semaglutide/liraglutide for MACE risk reduction. Monitor BP with naltrexone/bupropion and psychological side effects with phentermine/topiramate; tailor choices to comorbidities and tolerability.

Limitations

• Heterogeneity across trials and populations may affect pooled estimates
• Reliance on summary-level data limits exploration of individual patient modifiers

Future Directions

Head-to-head RCTs and IPD meta-analyses to refine comparative effectiveness and safety by patient subgroups and comorbidities; longer-term outcomes (maintenance, MACE, renal) and real-world adherence studies.