Incretin-Based Dual and Triple Agonists in Overweight or Obese Individuals: A Systematic Review and Meta-Analysis
- Design
- Meta-analysis · 3236 participants · Unknown 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.
In 10 trials (3,236 adults with obesity), tirzepatide, retatrutide and mazdutide lowered body weight more than placebo (mean difference -11.47; the abstract does not state the unit) and also lowered waist size, HbA1c and fasting glucose. They raised the risk of any side effect (RR 1.13), including gastrointestinal effects, stopping because of side effects (RR 1.96) and low blood sugar (RR 3.08); serious side effects did not differ (RR 0.87).
01Findings
What the study reported
- Drugs
- Tirzepatide, Retatrutide, Mazdutide
- 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)
- Sample size
- 3236
Study quality details
- Study design
- Meta-analysis
- Sample size
- 3236
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- not stated
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% confidence intervals (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
- Disclosure: The authors declare no conflict of interest.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Incretin-based dual and triple agonists have emerged as effective options for obesity management, offering enhanced weight loss through multi-receptor agonism. However, data on their efficacy and safety remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these emerging agents. A comprehensive literature search was conducted using PubMed, the Cochrane Library, and Google Scholar from inception to June 2025 to identify randomized controlled trials evaluating tirzepatide, retatrutide, or mazdutide in obese adults. Clinical outcomes were assessed using the random-effects model and pooled as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). A total of 10 randomized controlled trials, including 3236 participants, were analyzed. Incretin polyagonists significantly reduced body weight compared to placebo (MD -11.47; 95% CI: -14.00 to -8.95). Significant reductions were also observed in waist circumference (MD -9.40; 95% CI: -11.91 to -6.89), glycated hemoglobin (MD -0.96; 95% CI: -1.16 to -0.75), and fasting plasma glucose (MD -26.89 mg/dL; 95% CI: -33.48 to -20.30). However, the use of dual and triple agonists was associated with a higher risk of any adverse events (AEs) (RR 1.13; 95% CI: 1.08-1.19), including gastrointestinal AEs (nausea, vomiting, diarrhea, constipation), AEs leading to withdrawal (RR 1.96; 95% CI: 1.17-3.30), and hypoglycemic episodes (RR 3.08; 95% CI: 1.61-5.89). No significant difference was found in serious AEs (RR 0.87; 95% CI: 0.65-1.14). In conclusion, incretin-based polyagonists were associated with significant weight reduction and improved metabolic outcomes compared to placebo.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 30, 2026 | 41711462 first ingestion |