Risk of New-Onset Ischaemic and Haemorrhagic Stroke in Patients With Type 2 Diabetes With Chronic Kidney Disease on SGLT-2 Inhibitor Users: A Population-Based Cohort Study

Diabetes Metab Res Rev. 2026 Jan;42(1):e70122. doi: 10.1002/dmrr.70122.

Abstract

Background: Type 2 diabetes (T2D) and chronic kidney disease (CKD) increase the risk of ischaemic and haemorrhagic strokes. However, the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on reducing the risk of ischaemic and haemorrhagic strokes in patients with T2D and CKD remains unclear. Thus, this study was conducted to explore the role of SGLT2i in the prevention of ischaemic and haemorrhagic strokes.

Methods: In this retrospective cohort study, Cox regression analysis was employed to examine the hazard ratio (HR) between users and nonusers of SGLT2i on incident ischaemic and haemorrhagic strokes following 1:1 propensity score matching. The Kaplan-Meier method was used to determine the risk of study outcome over time between users and nonusers of SGLT2i. Finally, a sensitivity analysis of the HR was performed between users and nonusers of SGLT2i on incident ischaemic and haemorrhagic strokes after 1:2 sex and age matching.

Results: After 1:1 propensity score matching of patients by age, sex, T2D duration, and comorbidities, 107,819 users of SGLT2i and 107,819 nonusers were enrolled for analysis. SGLT2i therapy was associated with significantly reduced incidence of ischaemic and haemorrhagic strokes (HR 0.86, [95% CI, 0.81-0.90]; HR 0.80, [95% CI, 0.74-0.87]). Furthermore, the HR was even more significant in the sensitivity test for incident ischaemic and haemorrhagic strokes.

Conclusion: SGLT2i reduced the risk of incident ischaemic and haemorrhagic strokes among patients with T2D and CKD. The protective profile of the SGLT2i against incident ischaemic and haemorrhagic strokes makes it a clinical option for those with T2D with CKD.

Keywords: SGLT2 inhibitors; haemorrhagic stroke; ischaemic stroke; type 2 diabetes.

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Follow-Up Studies
  • Hemorrhagic Stroke* / epidemiology
  • Hemorrhagic Stroke* / etiology
  • Hemorrhagic Stroke* / prevention & control
  • Humans
  • Incidence
  • Ischemic Stroke* / epidemiology
  • Ischemic Stroke* / etiology
  • Ischemic Stroke* / prevention & control
  • Male
  • Middle Aged
  • Prognosis
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Retrospective Studies
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Stroke* / epidemiology

Substances

  • Sodium-Glucose Transporter 2 Inhibitors