GLP-1RAs for Ischemic Stroke Prevention in Patients With Type 2 Diabetes Without Established Atherosclerotic Cardiovascular Disease

Abstract

OBJECTIVE We assessed the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on ischemic stroke prevention in the Asian population with type 2 diabetes (T2D) without established cardiovascular disease. RESEARCH DESIGN AND METHODS This retrospective cohort study examined data obtained from the Taiwan National Health Insurance Research Database for the period from 1998 to 2018. The follow-up ended upon the occurrence of hospitalization for ischemic stroke. The median follow-up period was 3 years. The effect of GLP-1RA exposure time on the development of hospitalization for ischemic stroke was assessed. RESULTS The GLP-1RA and non–GLP-1RA user groups both included 6,534 patients. Approximately 53% of the patients were women, and the mean age was 49 ± 12 years. The overall risk of ischemic stroke hospitalization for GLP-1RA users was not significantly lower than that for GLP-1RA nonusers (adjusted hazard ratio [HR] 0.69 [95% CI 0.47–1.00]; P = 0.0506), but GLP-1RA users with a >251-day supply during the study period had a significantly lower risk of ischemic stroke hospitalization than GLP-1RA nonusers (adjusted HR 0.28 [95% CI 0.11–0.71]). Higher cumulative dose of GLP-1 RAs (>1,784 mg) was associated with significantly lower risk of ischemic stroke hospitalization. The subgroup analyses defined by various baseline features did not reveal significant differences in the observed effect of GLP-1RAs. CONCLUSIONS Longer use and higher dose of GLP-1 RAs were associated with a decreased risk of hospitalization for ischemic stroke among Asian patients with T2D who did not have established atherosclerotic cardiovascular diseases, but who did have dyslipidemia or hypertension.

Risk of stroke and retinopathy during GLP-1 receptor agonist cardiovascular outcome trials: An eight RCTs meta-analysis

“…The results of eight RCTs on CVOT outcomes of GLP-1RA in type 2 diabetic patients, which we included, showed that GLP-1RA treatment significantly reduced the risk of total stroke (~17%) and ischemic stroke (~17%) in type 2 diabetic patients, suggesting that GLP-1RA may have some protective effect in patients with cerebrovascular stenosis. Similar studies have been done in the past, A 2022 retrospective cohort study reported longer use and higher dose of GLP-1 RAs were associated with a decreased risk of hospitalization for ischemic stroke among Asian patients with T2DM who did not have established atherosclerotic cardiovascular diseases, but who did have dyslipidemia or hypertension (20). A net meta-analysis in 2021 showed GLP-1RA versus placebo Our findings indicate that GLP-1RA reduce the risk of stroke (OR 0.87, 95% CI 0.77 to 0.98; high-certainty evidence) (7).…”

Association of glucose-lowering drugs with incident stroke and transient ischaemic attacks in primary care patients with type 2 diabetes: disease analyzer database

“…Compared with DPP-4i, there was an indication for a lower HR for stroke (0.88; 0.77–1.01) in liraglutide users, although not statistically significant [ 14 ]. In a retrospective cohort study from the Taiwan National Health Insurance Research Database the risk of hospitalization for ischemic stroke for GLP-1RA users was also not statistically significantly lower than that for nonusers, although the HR indicated a protective effect (HR: 0.69; 95% CI 0.47–1.00) [ 15 ]. Thus, most previous observational studies from the US, Europe and Asia confirm our present results that GLP-1RA are associated with a lower HR for stroke after adjusting for confounders and modifiers in people with type 2 diabetes.…”

Incidence and Trends in Ischemic Stroke and Mortality in Patients with and Without Type 2 Diabetes in Taiwan 2000-2018

“…Using medications such as pioglitazone or glucagon-like peptide-1 receptor agonists (GLP-1 RA) to manage diabetes may be a proactive approach to prevent stroke development and improve prognosis. 30,31…”