Glucagonlike peptide‐1 receptor agonists versus dipeptidyl peptidase‐4 inhibitors in ischemic strokes with diabetes 2

Background and purpose Cardiovascular outcome trials demonstrate that glucagonlike peptide‐1 receptor agonists (GLP‐1RAs) reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes (T2D), whereas dipeptidyl peptidase‐4 inhibitors (DPP‐4is) have not shown cardiovascular benefits. We compared acute ischemic stroke (AIS) with T2D treated with either a GLP‐1RA or DPP‐4i prior to the index stroke. Methods This national cohort study included AIS patients with T2D from 2017 to 2020 in Denmark who were users of a GLP‐1RA or DPP‐4i. To be categorized as a user, we required at least 12 months of exposure and no concurrent treatment with another newer glucose‐lowering medication during the last 3 months prior to the index stroke. GLP‐1RA users were compared to users of DPP‐4i while adjusting for the calendar year of index stroke, age, sex, comorbidity, and socioeconomic factors. Results The study included 1567 AIS events with T2D; 593 were users of GLP‐1RA and 974 of DPP‐4i. The absolute risk of a very severe stroke was 2.4% (95% confidence interval [CI] = 1.2–3.7) in GLP‐1RA users and 6.1% (95% CI = 4.6–7.7) in DPP‐4i users. The corresponding adjusted risk ratio (aRR) of GLP‐1RA versus DPP‐4i was 0.49 (95% CI = 0.24–1.00). The aRRs of 30‐day and 365‐day mortality were 0.55 (95% CI = 0.32–0.94) and 0.72 (95% CI = 0.53–0.98), respectively. Conclusions The risk of a very severe stroke as well as the 30‐day and 365‐day poststroke mortality rates were lower among the AIS patients with comorbid T2D receiving GLP‐1RA prior to the index stroke compared to those receiving DPP‐4i. Hence, GLP‐1RA may improve stroke outcomes in comparison with DPP‐4i.