Emerging Anti-Obesity Medications for Obesity Management: A Systematic Review of Efficacy, Safety, and Outcomes

Background: The systematic review was done with an objective to assess efficacy and safety of anti-obesity medications (AOMs), FDA-approved and emerging, in various populations (older than 50 years of age, children, and individuals with type 2 diabetes [T2DM]); and to analyze cardiometabolic outcomes. Material and Methods: A detailed search was performed on several databases such as PubMed, Web of Science, DOAJ, Scopus and Embase, resulting in more than 7,000 potential citations. The inclusion criteria of the eight systematic reviews/meta-analyses were met and included hundreds of RCTs and real-world evidence studies. The data extracted included adverse event (AE) profiles, body weight changes and cardiometabolic outcomes. Results: All the pharmacological interventions showed better weight loss than the placebo treatment. Tirzepatide was the best of the drugs approved to date for absolute weight loss (WMD - 11.69 kg), whereas pipeline triple-agonist retatrutide had the highest mean weight loss (X WMD - 24.2% mean weight loss). The oral treatments included were orforglipron, which resulted in -14.7% weight loss at 36 weeks. The older adults ≥65 years old had significant reductions with semaglutide (8.1%). Cardiometabolic benefits were seen with tirzepatide's ability to lower systolic blood pressure by 5.74 mmHg and HbA1c by 1.27%. Gastrointestinal AEs occurred and were common, though: There was a higher risk of vomiting with tirzepatide (RR 4.95), and diarrhea was reported in 41% of participants in trials of semaglutide. Conclusion: Modern AOMs, notably GLP-1 and multi-receptor agonists like tirzepatide and retatrutide, achieve superior weight loss and significant cardiometabolic benefits across diverse populations. While highly efficacious, gastrointestinal side effects are common and often hinder real-world persistence.

Keywords: Cardiovascular diseases, orlistat, obesity management, semaglutide, weight loss.