Similar incidence of stroke with SGLT2 inhibitors and GLP-1 receptor agonists in real-world cohort studies among patients with type 2 diabetes

Abstract

Background

Stroke represents a major burden in patients with type 2 diabetes. Yet, this cerebrovascular complication has been less well studied than coronary artery disease and heart failure. Some cardiovascular outcome data suggested that sodium-glucose cotransporter 2 inhibitors (SGLT2is) exert a less pronounced protection against stroke compared with glucagon peptide-1 receptor agonists (GLP-1RAs) despite similar efficacy regarding major cardiovascular events (MACE-3 points). However, this conclusion was derived from indirect comparisons of placebo- controlled trials (RCTs).

Methods

The present comprehensive review analyses the effects of SGLT2is versus GLP-1RAs on nonfatal and fatal/nonfatal strokes in real-life studies carried out worldwide.

Results

A large majority of retrospective observational cohort studies (19 out of 21) failed to find any significant difference in the risk of stroke between the two pharmacological classes, independently of the presence of established cardiovascular disease. Available, yet limited, findings suggested that SGLT2is could be more efficacious against haemorrhagic than ischaemic strokes, in patients at risk for atrial fibrillation or with chronic kidney disease.

Conclusion

In contrast to what was reported in RCTs, most observational studies showed similar incidence of stroke in SGLT2i users versus GLP-1RA users. Because both indirect comparisons of RCTs and retrospective cohort studies have limitations, a head-to-head RCT comparing the effects on stroke of an SGLT2i versus a GLP-1RA is needed to draw any definite conclusion.