Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review
- Design
- Systematic review · 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] Glucagon-like peptide-1 receptor agonists demonstrate substantial weight loss in adults without diabetes, with an expanding range of therapeutic options, including oral and multiagonist therapies.
01Findings
What the study reported
- Drugs
- Semaglutide, Liraglutide, Orforglipron, Tirzepatide, Retatrutide, Cagrisema
- Route
- oral
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- 16 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)
Study quality details
- Study design
- Systematic review
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- 16 weeks
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI, -8
- 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] Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for weight management. [PURPOSE] To update our prior systematic review evaluating the efficacy and safety of GLP-1 RAs and co-agonists among adults with overweight or obesity without diabetes. [DATA SOURCES] MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from 5 October 2024 through 25 March 2026. [STUDY SELECTION] Randomized controlled trials ([RCTs] treatment duration ≥16 weeks). [DATA EXTRACTION] Two reviewers independently extracted data. [DATA SYNTHESIS] Thirty-eight RCTs (n = 25 816) were included, adding 14 new trials (n = 11 000) to the prior review. Among commercially available therapies, placebo-subtracted weight loss reached up to -5.8% (95% CI, -8.0% to -3.6%) for liraglutide, -14.8% (CI, -16.2% to -13.4%) for subcutaneous semaglutide, -14.3% (CI, -17.2% to -11.4%) for oral semaglutide, -12.4% (CI, -15.1% to -9.7%) for orforglipron, and -19.0% (CI, -21.6% to -16.4%) for tirzepatide. Numerically greater placebo-subtracted reductions were seen with emerging multiagonists, including -23.9% (CI, -29.3% to -18.5%) with amycretin and -22.1% (CI, -24.9% to -19.3%) with retatrutide. Gastrointestinal adverse events (AEs) remained common (GLP-1 RA vs. placebo: 76.0% vs. 40.1%). Discontinuation due to AEs was generally low (10.7% vs. 3.4%) but numerically higher with some oral agents. Serious AEs (6.5% vs. 5.2%) and deaths (0.1% vs. 0.0%) were rare, with no new safety signals identified. Head-to-head data showed greater weight loss with semaglutide and JNJ-64565111 than liraglutide and greater weight loss with tirzepatide and cagrilintide-semaglutide (CagriSema; Novo Nordisk) than semaglutide. [LIMITATIONS] Heterogeneity precluded quantitative synthesis. Safety outcomes were inconsistently reported. [CONCLUSION] Glucagon-like peptide-1 receptor agonists demonstrate substantial weight loss in adults without diabetes, with an expanding range of therapeutic options, including oral and multiagonist therapies. [PRIMARY FUNDING SOURCE] None. (PROSPERO: CRD42024505558).