Efficacy and Safety of Dual GLP-1/Glucagon Receptor Agonism in Overweight and Obesity: A Class-Specific Systematic Review and Meta-Analysis
- 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 obesity/overweight.
- 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.
Pooling 19 randomized trials of dual GLP-1/glucagon agonists (mazdutide, survodutide, cotadutide, efinopegdutide) in adults with overweight or obesity, the drugs reduced body weight (by about 6.7 kg, or 7.2%, more than control) and improved HbA1c, BMI, waist circumference, systolic blood pressure and triglycerides. Any adverse events were more common with the dual agonists (RR 1.16), while serious adverse events did not differ (RR 0.90). Longer head-to-head trials are needed to confirm durability and cardiovascular safety.
01Findings
What the study reported
- Drugs
- Mazdutide, Survodutide, Cotadutide, Efinopegdutide
- 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)
Study quality details
- Study design
- Meta-analysis
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- not stated
- 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% CIs
- 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
- not available in metadata
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Dual glucagon-like peptide-1/glucagon receptor (GLP-1/GCGR) agonists represent a novel obesity treatment class, but existing meta-analyses often conflate them with GIP-containing agents (tirzepatide, retatrutide) or restrict analysis to one or two drugs, leaving class-specific efficacy and safety incompletely characterized. [METHODS] We systematically searched PubMed, Embase, Cochrane Library, Scopus and ClinicalTrials.gov through 20 July 2026 for randomized controlled trials of mazdutide, survodutide, cotadutide, and efinopegdutide in adults with overweight/obesity (PROSPERO CRD420261456447). Random-effects meta-analysis pooled mean differences (MDs) and risk ratios (RRs) with 95% CIs; heterogeneity, subgroup, sensitivity, GRADE and publication bias analyses were performed. [RESULTS] Nineteen RCTs were included. Dual agonists significantly reduced absolute body weight (MD: -6.65 kg, moderate certainty), relative weight (MD: -7.15%), and increased likelihood of ≥ 5% weight loss (RR: 4.75, low certainty), with mazdutide and survodutide showing the largest effects. Significant improvements occurred in HbA1c, BMI, waist circumference, systolic blood pressure and triglycerides. Any adverse events were more frequent with dual agonists (RR: 1.16), while serious adverse events did not differ from controls (RR: 0.90, high certainty). [CONCLUSION] Dual GLP-1/GCGR agonists produce meaningful weight loss and metabolic improvements with acceptable short-term safety, though longer head-to-head trials are needed to confirm durability and cardiovascular safety.