Sodium-glucose co-transporter-2 inhibitors reduce the risk of new-onset stroke in patients with type 2 diabetes: A population-based cohort study

Tsung-Kun Lin; Yong-Hsin Chen; Jing-Yang Huang; Pei-Lun Liao; Mei-Chun Chen; Lung-Fa Pan; Gwo-Ping Jong

doi:10.3389/fcvm.2022.966708

Sodium-glucose co-transporter-2 inhibitors reduce the risk of new-onset stroke in patients with type 2 diabetes: A population-based cohort study

Front Cardiovasc Med. 2022 Aug 9:9:966708. doi: 10.3389/fcvm.2022.966708. eCollection 2022.

Authors

Tsung-Kun Lin^{1

2}, Yong-Hsin Chen^{3

4}, Jing-Yang Huang^{5

6}, Pei-Lun Liao⁵, Mei-Chun Chen¹, Lung-Fa Pan^{7

8}, Gwo-Ping Jong⁹

Affiliations

¹ Department of Pharmacy, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan.
² School of Pharmacy, National Defense Medical Center, Taipei City, Taiwan.
³ Department of Public Health, Chung Shan Medical University, Taichung, Taiwan.
⁴ Department of Occupational Safety and Health, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁵ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁶ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁷ Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
⁸ Department of Cardiology, Taichung Armed Forces General Hospital, Taichung, Taiwan.
⁹ Department of Internal Medicine, Chung Shan Medical University Hospital and Chung Shan Medical University, Taichung, Taiwan.

Abstract

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.

Keywords: SGLT2 inhibitor; concurrent medication; hemorrhagic stroke; ischemic stroke; new-onset stroke; type 2 DM.