A meta-analysis of 137 trials and nearly 57,000 patients found retatrutide produced the greatest weight loss (-26.6%) among 17 GLP-1 receptor agonists, followed by tirzepatide, with effectiveness varying by diabetes status and ethnicity.
-26.6% body weight with retatrutideThe triple-agonist retatrutide at 12 mg weekly produced the greatest weight reduction among 17 GLP-1 receptor agonists, though with a wide confidence interval reflecting early-stage data.
What the researchers found
Among 17 GLP-1 receptor agonists across 137 trials (310 treatment arms, 56,683 patients), retatrutide 12 mg weekly produced the largest weight reduction (mean -26.56%, 95% CI: -43.89% to -3.01%). Tirzepatide 15 mg weekly was consistently effective across all populations: -22.76% in non-diabetic overweight/obese patients, -11.09% in Caucasian T2D patients, and -4.97% in Asian T2D patients.
Higher baseline body weight predicted better weight loss outcomes, while higher baseline HbA1c predicted better glycemic improvements. For HbA1c reduction, tirzepatide 10 mg and oral orforglipron 10 mg were the most effective agents. The analysis also revealed marked differences in weight loss efficacy between diabetic and non-diabetic populations and between ethnic groups.
Why it matters
With the GLP-1 drug market exploding and multiple new agents in development, clinicians and patients need evidence-based comparisons to guide treatment selection. This is one of the most comprehensive quantitative comparisons to date, ranking 17 drugs head-to-head using model-based meta-analysis. The finding that weight loss varies significantly by diabetes status and ethnicity is clinically important for setting realistic expectations.
How the study worked
Systematic review and model-based meta-analysis of randomized controlled trials identified from PubMed, Cochrane CENTRAL, and Embase through January 2024. The 137 included trials were divided into three population groups: non-diabetic overweight/obesity, type 2 diabetes Caucasian, and type 2 diabetes Asian. Five mathematical models were used for longitudinal analysis of body weight change and HbA1c change. Covariates including baseline body weight and HbA1c were evaluated for their influence on outcomes.
What this study cannot tell us
Retatrutide's confidence interval was very wide (-43.89% to -3.01%), reflecting limited trial data for this newer agent. The analysis pooled data across trials with different designs, durations, and populations, which introduces heterogeneity. The three population subgroups are broad categories that don't capture the full diversity of patient characteristics. Data cutoff was January 2024, so more recent trial results are not included. Safety and tolerability were not compared in this analysis.
How to read the evidence
This is a systematic review and model-based meta-analysis of 137 randomized controlled trials — the highest level of evidence synthesis. The large patient pool (56,683) and rigorous mathematical modeling strengthen the findings, though some agents (especially retatrutide) have limited trial data contributing to wider confidence intervals.
When this study was published
Published in 2025 with data through January 2024, this is highly current. However, the GLP-1 drug landscape is evolving rapidly, and newer data from ongoing retatrutide and orforglipron phase 3 trials may shift the rankings.
The bigger picture
The GLP-1 receptor agonist class has expanded from simple single-target drugs like liraglutide to multi-target agonists like tirzepatide (GLP-1/GIP dual agonist) and retatrutide (GLP-1/GIP/glucagon triple agonist). This meta-analysis captures that evolution, showing that multi-target peptides are pulling ahead in efficacy. The racial/ethnic differences in weight loss response highlight an important but often overlooked aspect of precision medicine in obesity treatment.
Questions still open
- Will retatrutide's impressive weight loss data hold up in larger phase 3 trials with tighter confidence intervals?
- What biological mechanisms explain why patients with type 2 diabetes lose less weight on GLP-1 agonists than non-diabetic patients?
- How should clinicians factor in the ethnic differences in GLP-1 weight loss response when prescribing these medications globally?
Common questions
Which GLP-1 drug causes the most weight loss?
Why do people with diabetes lose less weight on GLP-1 drugs than people without diabetes?
Read the original research
Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis.
Diabetes technology & therapeutics, 27(6), 422-429
Citation
Zhang, Shaolong; Yu, Boran; Xu, Jiamin; Jin, Siyao; Li, Yanming; Bing, Hao; Li, Jueyu; Ma, Xiangyu; Zhang, Xianhua; Zhao, Libo. (2025). Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis.. Diabetes technology & therapeutics, 27(6), 422-429. https://doi.org/10.1089/dia.2024.0533