GLP-1 receptor agonists for weight loss: A systematic review and meta-analysis of randomized controlled trials.
This systematic review and meta-analysis pooled evidence from 21 randomized controlled trials (n = 7,024 participants) to evaluate the weight-loss efficacy of GLP-1 receptor agonists (GLP-1 RAs) compared with placebo or active comparators. Across 16 placebo-controlled trials, the study found that a substantially higher proportion of participants achieved weight loss with GLP-1-based agents (78.54%) than with placebo (26.53%), yielding a pooled odds ratio of 11.37 (95% CI: 8.10–15.98). A frequentist network meta-analysis using SUCRA rankings suggested that tirzepatide and semaglutide demonstrated the greatest relative efficacy among agents evaluated. The authors concluded that GLP-1 RAs significantly increase the likelihood of weight loss and support their role in clinical obesity management. Notable limitations include the use of a fixed-effect model despite potential heterogeneity across trials, a binary primary endpoint (any weight loss) rather than magnitude of weight loss, the absence of a pre-registered protocol, and inclusion criteria restricted to the past five years in English only. These methodological choices may affect the precision and generalizability of the pooled estimates.
Why this grade: The study synthesizes 21 RCTs in human participants (n = 7,024), the highest level of primary study design, though the absence of a pre-registered protocol and use of a fixed-effect model introduce some methodological concerns.
Background Obesity is a complex condition marked by excessive body fat, linked to comorbidities such as type 2 diabetes and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for diabetes, are increasingly used for weight management. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (PubMed, last 5 years, English language) evaluating GLP-1-based pharmacotherapies versus placebo or active comparators for weight loss. The primary endpoint was the proportion of participants achieving any weight loss during follow-up. Pooled odds ratios were estimated using a fixed-effect model with 95% confidence intervals; heterogeneity was quantified with I2. A frequentist network meta-analysis generated SUCRA rankings. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. No protocol was registered. Results Twenty-one trials met the inclusion criteria (n = 7024 in pairwise analyses). Across 16 placebo-controlled trials, a higher proportion of participants achieved weight loss with GLP- 1-based agents than with placebo: 78.54% (3231/4114) versus 26.53% (772/2910); pooled odds ratio: 11.37 (95% confidence interval: 8.10-15.98), P Conclusion GLP-1 receptor agonists significantly increase the likelihood of weight loss versus placebo, with tirzepatide and semaglutide demonstrating the greatest relative efficacy among agents evaluated. These findings support GLP-1-based therapy as an effective component of clinical obesity management.
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