Physicians' Academy for Cardiovascular Education

Fewer first strokes in T2DM patients after GLP-1RA treatment

Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6

Literature - Strain WD, Frenkel O, James MA, et al. - Stroke. 2022 May 18;101161STROKEAHA121037775. doi: 10.1161/STROKEAHA.121.037775

Introduction and methods


As DM patients are more likely to have a stroke at a younger age, with worse outcomes and a higher recurrence risk than those without DM [1,2], stroke prevention is highly important in DM. Based on growing evidence, GLP-1RAs may reduce stroke risk in T2DM patients, even beyond glycemic control [3-8].

Aim of the study

The authors aimed to examine the effect of the GLP-1RA semaglutide on stroke risk, stratified by stroke subtype, in T2DM patients at high CVD risk.


In an exploratory post-hoc analysis, data from two global phase 3 RCTs were pooled: the SUSTAIN 6 and PIONEER 6 trial. In the SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes), patients were randomized to once-weekly 0.5 or 1 mg semaglutide subcutaneous or placebo [9], whereas once-daily 14 mg semaglutide orally or placebo was used in the PIONEER (Peptide Innovation for Early Diabetes Treatment) 6 study [10]. Inclusion criteria for both trials were: (1) T2DM; and (2) age ≥50 years with established CVD (f.e., MI, stroke, TIAs), chronic HF, or chronic kidney disease; or age ≥60 years with CVD risk factors.


The main outcomes were time to first occurrence of any type of stroke (fatal and nonfatal) and stroke subtypes (ischemic, hemorrhagic, or unknown). In a subgroup analysis, treatment effects on time to occurrence of any stroke were assessed across different subgroups, including prior stroke, prior MI or stroke, prior AF, age, sex, eGFR and systolic blood pressure. In addition, the impact of prior stroke on the effect of semaglutide versus placebo on time to first MACE was investigated.

Main results

Stroke risk

Subgroup analysis

MACE risk


In T2DM patients with high CVD risk, semaglutide reduced the risk of any first stroke compared with placebo, regardless of prior stroke. Semaglutide’s effect was mainly due to a lower risk of small-vessel occlusion.


Show references

Find this article online at Stroke

Share this page with your colleagues and friends: