Comparative efficacy and safety of glucagon-like peptide 1 based drugs for weight loss in adults with overweight or obesity without diabetes: network meta-analysis of randomised controlled trials
- Design
- Meta-analysis · 214 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 1 · automatic, not yet reviewed by a person · Sep 13, 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.
[Auto, unreviewed; quoted from abstract conclusions] In adults with overweight or obesity without diabetes, next generation incretin based treatments achieved greater weight loss than conventional GLP-1 receptor agonists. Differences in tolerability, limited head-to-head evidence, and residual uncertainty, however, should be considered when interpreting comparative treatment effects.
01Findings
What the study reported
- Drugs
- Semaglutide, Tirzepatide, Retatrutide, Mazdutide, Cagrisema
- Treatment duration
- 12 weeks
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- 12 weeks
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- excluded (no diabetes)
- Sample size
- 214
Study quality details
- Study design
- Meta-analysis
- Sample size
- 214
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- 12 weeks
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% confidence interval -25
- 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
- All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Natural Science Foundation of China for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[OBJECTIVE] To compare the efficacy and safety of glucagon-like peptide 1 (GLP-1) based drug treatments for weight loss in adults with overweight or obesity without diabetes. [DESIGN] Network meta-analysis of randomised controlled trials. [DATA SOURCES] Embase, PubMed (Medline), and Web of Science, 1 January 2000 to 6 March 2026. [ELIGIBILITY CRITERIA FOR SELECTING STUDIES] Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks. Excluded were trials that enrolled participants with diabetes, or where diabetes status could not be clearly determined. [RESULTS] 58 trials of 24 214 participants were analysed. Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%). Conventional GLP-1 receptor agonists showed more modest effects. Similar patterns were seen for waist circumference and lipid outcomes. Treatment rankings suggested a probabilistic hierarchy favouring next generation incretin based treatments, although confidence intervals overlapped for several comparisons. Low certainty evidence suggested higher rates for discontinuing treatment with danuglipron and retatrutide, whereas mazdutide showed better tolerability. [CONCLUSIONS] In adults with overweight or obesity without diabetes, next generation incretin based treatments achieved greater weight loss than conventional GLP-1 receptor agonists. Differences in tolerability, limited head-to-head evidence, and residual uncertainty, however, should be considered when interpreting comparative treatment effects. [STUDY REGISTRATION] PROSPERO CRD420261279841.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 42688617 first ingestion |