New Drug Demonstrates Greatest Weight Loss Among GLP-1 Therapies: Findings from a Systematic Review

A recently published systematic review of 26 randomized controlled trials (RCTs), encompassing data from over 15,000 patients, evaluated the efficacy and safety of glucagon-like peptide-1 (GLP-1) receptor agonists and co-agonists for weight loss among adults without diabetes. The findings indicate that the experimental agent Retatrutide achieved the greatest reduction in body weight—a 22% loss from baseline after 48 weeks of treatment.

Comparative results from other GLP-1-based treatments include:

- Tirzepatide (15 mg, once-weekly injection): approximately 18% weight loss after 72 weeks

- Semaglutide (2.4 mg, once-weekly injection): approximately 14% weight loss after 68 weeks

- Liraglutide (3 mg, once-daily injection): up to 6% weight loss after 26 weeks

Importantly, the review did not identify any head-to-head trials among these agents. The authors caution that direct comparisons between treatments should be interpreted carefully, given differences in study design, populations, control groups, and durations.

Gastrointestinal adverse events were the most frequently reported side effects across all treatments, with 60% to 80% of participants experiencing symptoms such as nausea, diarrhea, constipation, and vomiting. Treatment discontinuation due to adverse events ranged from 6% to 26%.

Reference:

Moiz, A., Filion, K. B., Toutounchi, H., et al. Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes: A Systematic Review of Randomized Controlled Trials. Annals of Internal Medicine. Published online January 7, 2025. doi:10.7326/ANNALS-24-01590