THU338 Risks Of Stroke, Its Subtypes And Atrial Fibrillation Associated With Glucagon-like Peptide 1 Receptor Agonists Versus Sodium-glucose Cotransporter 2 Inhibitors: A Real-world Population-based Study In Hong Kong
Authors: Lui David , Tang Eric , Wu Tingting , Au Ivan , Ho Lee Chi , Cho Woo Yu , CB Tan Kathryn , Wong Carlos 
Published: October 2023

Abstract
Disclosure: D. Lui: None. E. Tang: None. T. Wu: None. I. Au: None. C. Lee: None. Y. Woo: None. K.C. Tan: None. C. Wong: None.
Objectives: There are limited data on head-to-head comparative risk of stroke between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Such a comparison may provide further insights in the selection of appropriate anti-diabetic agents. We compared risk of stroke with its subtypes and incident atrial fibrillation (AF) between them in a population-based cohort. Methods: A population-based cohort of adult patients (aged 18 years or above) with type 2 diabetes between 2008 and 2020 were identified from the electronic health records of Hong Kong Hospital Authority. Patients who received SGLT2i or GLP-1RA were matched pairwise by propensity score. The index date of each patient was set at the date of SGLT2i or GLP-1RA initiation. Patients with end-stage kidney disease or co-initiation of SGLT2i and GLP-1RA at the index date were excluded. The primary outcome was all events of stroke, consisting of hemorrhagic and ischemic stroke. Secondary outcomes included hemorrhagic stroke, ischemic stroke, incident AF, and cardioembolic stroke. Each patient was observed from the index date until the occurrence of events, death, treatment cross-over, or end-of-study (31 December 2020), whichever was earlier. Risks of stroke and AF were evaluated by hazard ratios (HRs) from the Cox proportional hazard regression models. Results: A total of 5,840 patients (2,920 SGLT2i users; 2,920 GLP-1RA users) were included (mean age 55.5 years, 56.1% men, mean HbA1c 8.9% and duration of diabetes 13.7 years). Upon median follow-up of 17 months (IQR: 8-34), there were 111 events of stroke. SGLT2i users had comparable risk of all stroke as GLP-1RA users (HR=1.46, 95%CI 0.99-2.17, p=0.058). SGLT2i users had higher risk of ischemic stroke (HR=1.53, 95%CI 1.01-2.33, p=0.044) but similar risk of hemorrhagic stroke (HR=1.29, 95%CI: 0.53-3.14, p=0.582) compared to GLP-1RA users. Although SGLT2i was associated with lower risk of incident AF (HR=0.43, 95%CI 0.23-0.79, p=0.006), risk of cardioembolic stroke was similar (HR=1.40, 95%CI: 0.62-3.17, p=0.414). Subgroup analyses showed no significant interaction between subgroups by age, sex, glycemic control and history of AF. However, patients with history of stroke appeared to benefit more from GLP-1RA use (p for interaction=0.043) than those without history of stroke. Patients with shorter duration of diabetes (&lt;10 years) also appeared to benefit more from GLP-1RA use than those with longer duration of diabetes (p for interaction=0.017). Conclusions: Our real-world study demonstrated that GLP-1RA use was associated with lower risk of ischemic stroke, despite the association between SGLT2i use and lower risk of incident AF. There was no significant difference in hemorrhagic stroke risk. GLP-1RA may be the preferred agent for patients with type 2 diabetes at risk of ischemic stroke.
Presentation: Thursday, June 15, 2023