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Do SGLT2 inhibitors and GLP-1 receptor agonists modulate differently the risk of stroke ? Discordance between

André J Scheen1

  • 1Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liège University, Liège, Belgium; Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liège, Liège, Belgium.

Diabetes & Metabolism
|September 7, 2023
PubMed

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may offer better stroke protection than sodium-glucose cotransporter 2 inhibitors (SGLT2is) in type 2 diabetes patients. Network meta-analyses suggest a higher stroke risk with SGLT2is, but real-world studies show no significant difference.

Area of Science:

  • Endocrinology
  • Cardiology
  • Neurology

Background:

  • Stroke is a significant complication in type 2 diabetes, often overshadowed by cardiovascular and renal risks.
  • Existing research suggests potential differences in stroke protection between GLP-1RAs and SGLT2is, but lacks direct comparative trials.

Purpose of the Study:

  • To comprehensively compare the effects of SGLT2is versus GLP-1RAs on stroke incidence.
  • To evaluate stroke risk based on network meta-analyses of RCTs and real-world observational studies.

Main Methods:

  • Network meta-analyses of randomized controlled trials (RCTs) comparing SGLT2is and GLP-1RAs against placebo.
  • Analysis of real-life observational cohort studies examining stroke risk between the two drug classes.

Main Results:

  • Network meta-analyses indicated a slightly higher stroke incidence with SGLT2is compared to GLP-1RAs (significant in 11/13 analyses).
  • The majority of observational studies (19/21) found no significant difference in stroke risk between SGLT2is and GLP-1RAs.
  • Preliminary findings suggest SGLT2is might be more effective against hemorrhagic than ischemic strokes, particularly in patients with atrial fibrillation or chronic kidney disease.

Conclusions:

  • Evidence from RCT meta-analyses suggests a potential increased stroke risk with SGLT2is versus GLP-1RAs.
  • Real-world data largely contradicts this, showing comparable stroke risk between the two classes.
  • Further research is needed to clarify the specific benefits of SGLT2is in certain patient subgroups.
Keywords:
GLP-1 receptor agonistRandomised control trialReal-world evidenceSGLT2 inhibitorStrokeType 2 diabetes

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