GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Pooled result · Adverse cerebrovascular outcomesResult — go to the resultRelative risk 0.83 95% CI 0.76–0.91Authors' conclusion
GLP-1RAs, particularly longer-acting formulations, reduced ischemic cerebrovascular events in T2DM. Observed benefits were significantly higher in patients with shorter T2DM duration and higher eGFR.
Study context
- Population
- Adults with T2D in randomized controlled trials (RCTs) ≥24 weeks; 57% male; median age 58 years, BMI 32 kg/m², T2D duration 9 years, treatment duration 52 weeks
- Participants
- 74,148 adults28 RCTs
- Comparison
- GLP-1 RA vs placebo/active comparator
- Outcome
- Adjudicated adverse cerebrovascular outcomes:
- Ischemic/hemorrhagic stroke
- Transient ischemic attacks (TIA)
Methodological detailsfixed-effects model, GRADE framework, RCTs ≥24 weeks
- Fixed-effects model
- GRADE framework
- RCTs ≥24 weeks
Pooled result
Adverse cerebrovascular outcomes
Relative risk
0.83
95% CI 0.76–0.91
GLP-1RAvs Placebo/active comparator
RR 0.83 (95% CI 0.76–0.91)
As reported in the abstract
Further pooled results
| Outcome | RR (95% CI) | |
|---|---|---|
| Nonfatal stroke (cardiovascular outcome trials, n = 8)GLP-1RAvs PlaceboI2 = 0% | 0.85 (0.76–0.94) | |
| Fatal stroke (cardiovascular outcome trials, n = 8)GLP-1RAvs PlaceboI2 = 0% | 0.80 (0.61–1.05) | |
| Ischemic stroke (12 RCTs)GLP-1RAvs Placebo/active comparatorI2 = 0% | 0.73 (0.60–0.89) | |
| Composite of ischemic stroke/TIA (16 RCTs)GLP-1RAvs Placebo/active comparatorI2 = 0% | 0.76 (0.65–0.90) | |
| Hemorrhagic stroke (3 RCTs)GLP-1RAvs Placebo/active comparatorI2 = 0% | 0.92 (0.51–1.64) | |
| 0.512Relative risk (log scale) |
Subgroups: baseline eGFR, diabetes duration, individual drugs
- Treatment benefits differed by baseline eGFR and diabetes duration
- P for interaction < 0.1
- Benefits statistically significant for dulaglutide, subcutaneous/oral semaglutide
- P < 0.05
- Sensitivity analysis excluding shorter-acting lixisenatide eliminated heterogeneity between individual GLP-1RA effects
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. Published 17 February 2023. doi:10.
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