GLP-1 Receptor Agonists and Noncardiometabolic Outcomes: An Umbrella Review of Meta-Analyses
Authors' conclusion
In this umbrella review of meta-analyses, evidence for most noncardiometabolic outcomes associated with GLP-1 RAs was of lower certainty. Potential safety signals were observed for gastrointestinal AEs, while suggested protective associations with respiratory diseases and serious infections require further confirmation.
Study context
- Population
- Meta-analyses of RCTs of GLP-1 RAs, populations mainly T2D (43 [71.7%]) and obesity (20 [33.3%]); follow-up 3 months to 5.4 years or longer60 meta-analyses
- Participants
- 3,580,616 participants1,751 RCTs
- Comparison
- GLP-1 RAs vs comparators in RCTs
- Outcome
- Noncardiometabolic outcomes across gastrointestinal, AE, cancer, fracture, respiratory, neurologic, psychiatric, hepatic and endocrine domains
Methodological detailsrandom-effects reanalysis, AMSTAR 2 quality appraisal, GRADE certainty, prespecified credibility criteria, PRISMA, Data extracted by 2 independent reviewers at meta-analysis and individual study level
- Random-effects reanalysis
- AMSTAR 2 quality appraisal
- GRADE certainty
- Prespecified credibility criteria
- PRISMA
- Data extracted by 2 independent reviewers at meta-analysis and individual study level
Pooled result
As reported in the abstract
Noncardiometabolic outcomes:
- GI
- AE
- Cancer
- Fracture
- Respiratory
- Neurologic
- Psychiatric
- Hepatic
- Endocrine domains
- Nausea, higher odds: OR (95% CI); GRADE high quality
- 2.47 (1.84-3.34)
- Vomiting, higher odds: OR (95% CI); GRADE moderate quality
- 2.78 (1.91-4.06)
- Diarrhea, higher odds: OR (95% CI); GRADE high quality
- 1.94 (1.52-2.49)
- Serious infections, possible protective association: OR (95% CI); GRADE high quality
- 0.89 (0.87-0.92)
- Incident respiratory disease, suggestive association: OR
- 0.85 (0.80-0.92) (95% CI)
- Gallbladder or biliary disease: OR (95% CI); did not meet stringent credibility thresholds, exploratory
- 1.34 (1.16-1.55)
Original publication
GLP-1 Receptor Agonists and Noncardiometabolic Outcomes: An Umbrella Review of Meta-Analyses. JAMA Netw Open. Published 2 March 2026. doi:10.
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