Efficacy and Safety of Dual GLP-1/Glucagon Receptor Agonism in Overweight and Obesity: A Class-Specific Systematic Review and Meta-Analysis.
Dual GLP-1/glucagon receptor agonists can lead to significant weight loss and metabolic improvements, but further research is needed to confirm long-term safety and effectiveness.
Where it sits
this study against the rest of the mazdutide (ibi362) corpusSummary and findings
This systematic review and meta-analysis evaluated the efficacy and safety of dual GLP-1/glucagon receptor agonists, including mazdutide, in adults with overweight and obesity. The analysis included nineteen randomized controlled trials. Significant reductions in body weight and improvements in metabolic parameters were observed.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.