Background: Glucagon-like peptide 1 receptor (GLP-1R) agonists, a novel class of antidiabetic agents, have been reported to exert neuroprotective effects in experimental stroke models, especially if treatment starts before stroke.

Aims: We aimed to assess available data regarding the risk of stroke in diabetic individuals treated with GLP-1R agonists.

Methods: We conducted a meta-analysis of randomized, double blinded, placebo-controlled trials (RCTs) involving GLP-1R agonists with cardiovascular outcomes and/or safety as primary endpoints.

Results: Five eligible multicenter (n=42,358) prospective double-blinded RCTs (ELIXA, LEADER, SUSTAIN, EXSCEL and HARMONY) were identified up to October 2018 and included in the present meta-analysis. The pooled analysis showed a significant reduction by 13% in the risk of total stroke from treatment with GLP-1R agonists vs. placebo (risk ratio, RR: 0.87, 95% confidence interval, CI: 0.78 - 0.98, p = 0.021). No significant heterogeneity among trials was detected (Q-value = 4.094, p = 0.393, I2 = 2.307%). When only fatal stroke was included (this applied for ELIXA, LEADER, EXSCEL and HARMONY trials), active treatment resulted in a non-significant reduction by 16% compared with placebo (RR: 0.84, 95% CI: 0.60 - 1.17, p = 0.29) without any significant heterogeneity (Q value = 2.12, p = 0.548, I2 = 0%).

Conclusions: Available data from RCTs dedicated to cardiovascular safety support the promising findings from previous experimental studies indicating protective effects of treatment with GLP-1R agonists against stroke.

01 - GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS PROTECT AGAINST STROKE IN PATIENTS WITH DIABETES: A SYSTEMATIC REVIEW AND META-ANALYSIS