Sodium-glucose co-transporter-2 inhibitors reduce the risk of new-onset stroke in patients with type 2 diabetes

Background: Epidemiological evidence suggests the association of diabetes with an increased risk of stroke. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on new-onset stroke (NOS), but the results are inconsistent. Objectives: To determine the association between the use of SGLT2 inhibitors and NOS in patients with type 2 diabetes mellitus (DM). Methods: We conducted a retrospective longitudinal cohort study based on the Taiwan Health Insurance Review and Assessment Service database (2016–2019). The primary outcome of the assessment was the risk of incident stroke by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was applied to estimate the adjusted HR of NOS. Subgroup analysis was also conducted. Results: Among the 232,101 eligible patients with type 2 DM aged ≥ 20 years, SGLT2-inhibitor users were compared with non-SGLT2-inhibitor users based on age, sex, and the duration of type 2 DM matching at a ratio of 1:2. The event rate per 10 000 person-months was 9.20 (95% CI 8.95 to 9.45) for SGLT2-inhibitor users and 10.5(10.3–10.6) for non-SGLT2-inhibitor users. There was a decreased risk of NOS for SGLT2-inhibitor users (adjusted HR 0.85, 95% CI 0.82–0.88) compared with non-SGLT2-inhibitor users. Results for the propensity score-matched analyses showed similar results (adjusted HR 0.87, 95% CI 0.84–0.91 for both SGLT2-inhibitor users and non-SGLT2-inhibitor users). Conclusion: The risk of developing NOS was lower in patients with SGLT2-inhibitor users than in non-SGLT2-inhibitor users. The decreased risk of NOS in patients with type 2 DM was greater among patients with concurrent use of statins, biguanides, thiazolidinediones, and glucagon-like peptide-1 receptor agonists. We, therefore, suggest that the long-term use of SGLT2 inhibitors may help reduce the incidence of NOS in patients with type 2 DM.