Protection against stroke with glucagon-like peptide 1 receptor agonists: a systematic review and meta-analysis

In experimental stroke models pretreatment with the newly introduced antidiabetic agents, glucagon-like peptide 1 receptor (GLP-1R) agonists, has been shown to exert neuroprotective effects. Published evidence with regard to the effect of treatment with GLP-1R agonists on the risk of stroke was evaluated. Data from prospective randomized placebo-controlled trials up to October 2018 involving GLP-1R agonists which reported cardiovascular outcomes as primary end-points of efficacy and/or safety were meta-analysed. Five eligible multicentre randomized placebo-controlled trials (ELIXA, LEADER, SUSTAIN, EXSCEL and HARMONY) were included. The pooled analysis (n = 42 358) showed a significant reduction by 13% in the risk of total stroke from treatment with GLP-1R agonists versus placebo (risk ratio 0.87, 95% confidence interval 0.78-0.98, P = 0.021) with no significant heterogeneity between trials (Q = 4.094, P = 0.393, I²  = 2.307%). When only fatal stroke was included (this applied for the ELIXA, LEADER, EXSCEL and HARMONY trials), active treatment was associated with a non-significant reduction by 16% compared with placebo (risk ratio 0.84, 95% confidence interval 0.60-1.17, P = 0.29). The findings of this meta-analysis support the evidence from earlier experimental studies calling attention to potential 'stroke protective' effects from treatment with GLP-1R.