Comparative Efficacy and Safety of Glucagon Receptor Agonists on Metabolic Outcomes: A Network Meta-Analysis of Randomised Controlled Trials
- Design
- Meta-analysis · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Synthesis of studies conducted predominantly in people with type 2 diabetes.
- Could weight loss explain it?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 3 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
A network meta-analysis of 14 trials in people with type 2 diabetes, overweight or obesity compared four glucagon-receptor drugs. Retatrutide gave the largest weight loss (about 13 kg more than placebo), followed by survodutide (about 11 kg) and mazdutide (about 6 kg); cotadutide's weight effect was not significant. Retatrutide was the only drug that significantly lowered HbA1c. Mazdutide was best tolerated, while retatrutide and cotadutide were less well tolerated.
01Findings
What the study reported
- Drugs
- Retatrutide, Survodutide, Mazdutide, Cotadutide
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- mixed: trials in people with type 2 diabetes, overweight or obesity
Study quality details
- Study design
- Meta-analysis
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- not stated
- Outcome type
- intermediate
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI [-18
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- The authors declare no conflicts of interest.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[INTRODUCTION] Glucagon receptor agonists (GRAs) are an emerging class of therapies for obesity and type 2 diabetes, demonstrating encouraging metabolic and weight-reducing effects. Several investigational GRA-based agents, including retatrutide, cotadutide, mazdutide, and survodutide, have reported promising results across early and mid-phase clinical trials. This comprehensive meta-analysis evaluates the efficacy and safety of these agents in individuals with type 2 diabetes, overweight, or obesity. [METHODS] PubMed, Cochrane, Embase, and Scopus databases were systematically searched. Fourteen randomised controlled trials meeting the inclusion criteria were analysed using frequentist network meta-analysis. Random-effects models were applied to assess mean differences (MD) in weight change, both absolute and percent changes, HbA1c, adverse events, and discontinuation due to adverse events. Heterogeneity was quantified using the I2 statistic. [RESULTS] Retatrutide demonstrated the greatest weight reduction versus placebo (MD -13.44 kg; 95% CI [-18.38, -8.51]), followed by survodutide (MD -10.74 kg; 95% CI [-15.68, -5.80]) and mazdutide (MD -6.47 kg; 95% CI [-10.71, -2.24]). Cotadutide showed the smallest and nonsignificant effect (MD -3.41 kg; 95% CI [-11.63, 4.81]). Regarding HbA1c reduction, retatrutide showed the largest effect, followed by survodutide, mazdutide, and cotadutide; however, only the effect of retatrutide reached statistical significance. In terms of safety, mazdutide demonstrated the most favourable tolerability profile, whereas retatrutide and cotadutide were associated with comparatively lower tolerability. [CONCLUSIONS] Retatrutide and survodutide exhibit the most favourable efficacy profiles for obesity and T2DM, with acceptable safety. These findings support their potential clinical use and highlight the need for future head-to-head trials.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 30, 2026 | 41787737 first ingestion |