GLP-1 drugs stand out for stroke risk reduction in diabetes

Clinical takeaway: When cerebrovascular risk is an important treatment consideration in type 2 diabetes, GLP-1 receptor agonists may offer an advantage over SGLT2 and DPP-4 inhibitors, although these observational findings should not override each drug class’s broader cardiovascular and renal benefits.

Type 2 diabetes substantially increases ischemic stroke risk, but evidence has differed on whether newer glucose-lowering drug classes provide cerebrovascular protection. Randomized trials have generally supported a stroke benefit with GLP-1 receptor agonists while showing neutral effects for SGLT2 and DPP-4 inhibitors.

In a nationwide longitudinal cohort study, investigators analyzed 171,917 adults with type 2 diabetes newly registered in the Swedish National Diabetes Register from 2013 through 2019, excluding those with previous stroke. Over a mean 3 years of follow-up, 2,734 participants (1.59%) experienced an ischemic stroke and 428 (0.25%) a hemorrhagic stroke.

After accounting for changes in treatment, clinical characteristics and concomitant medications over time, GLP-1 receptor agonist use was associated with a 54% lower hazard of ischemic stroke and a 49% lower hazard of total stroke versus nonuse. No clear association emerged for hemorrhagic stroke. By contrast, SGLT2 inhibitor and DPP-4 inhibitor use was not clearly associated with ischemic, hemorrhagic or total stroke.

The researchers also reviewed 91 prior meta-analyses. Their findings tracked closely with randomized-trial evidence, which has generally shown stroke protection with GLP-1 receptor agonists but neutral effects with SGLT2 and DPP-4 inhibitors; observational studies of SGLT2 inhibitors have been less consistent.

The authors cautioned that residual confounding and other biases inherent to observational studies could have contributed to the particularly large effect observed with GLP-1 therapy. Still, they concluded that “GLP-1RA may be considered as part of strategies to reduce cerebrovascular risk in individuals with type 2 diabetes.”

Source: Mavridis A, et al. (2026 Oct) eClinicalMedicine. The effect of SGLT2 inhibitors, GLP-1 receptor agonists, or DPP-4 inhibitors on stroke risk in type 2 diabetes: a nationwide longitudinal cohort study in Sweden with contextualisation analysis