GLP-1 Receptor Agonists for Stroke Prevention in Type 2 Diabetes or Obesity

What is the efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists for stroke prevention in patients with type 2 diabetes or obesity?

Patients with type 2 diabetes who took GLP-1 receptor agonists had a 0.4% lower absolute risk of nonfatal stroke compared with patients who took a placebo, with the number needed to treat (NNT) of 257 over 3.6 years. (Strength of Recommendation [SOR]: A, systematic review and meta-analysis.) In adults with obesity but not type 2 diabetes, GLP-1 receptor agonist treatment is associated with a 47% lower rate of stroke compared with no GLP-1 receptor agonist treatment. (SOR: B, single large retrospective cohort study.)

A 2024 systematic review and meta-analysis of 11 randomized controlled trials (N = 82,140) examined the effect of GLP-1 receptor agonists on stroke risk, including in patients with type 2 diabetes. Patients were adults, and 35% were female, 73% identified as Caucasian, 78% had type 2 diabetes, 19% had heart failure, and 17% (eight trials, n = 11,340) experienced a previous stroke. The intervention included one of seven GLP-1 receptor agonists taken orally or by injection weekly or daily for an average duration of 3.6 years. The comparator was matching placebo. The primary outcome was reduction of stroke risk. Secondary outcomes included reduction in the risks of nonfatal and fatal stroke. A secondary analysis investigated stroke reduction in patients with diabetes compared with those without diabetes.¹

The overall stroke risk was lower in the GLP-1 receptor agonist group vs the placebo group, with an NNT of 200 (risk ratio [RR] = 0.85; 95% CI, 0.77–0.93). Overall, GLP-1 receptor agonists also were associated with a significantly decreased risk of nonfatal stroke vs placebo, with an NNT of 250 (RR = 0.87; 95% CI, 0.79–0.95). However, there was no significant difference in the risk of fatal stroke.¹

In a subgroup analysis, the stroke risk in patients with type 2 diabetes was significantly lower in patients taking GLP-1 receptor agonists, with an NNT of 257 (RR = 0.86; 95% CI, 0.77–0.95). No difference was found in patients without type 2 diabetes. Limitations included use of various treatment regimens and medications, and no evaluation of safety outcomes or adverse reactions. The standard of care for adding other medications for cardiovascular event prevention differed between the studies, and one study had a high rate of early treatment discontinuation.¹

A 2024 retrospective, observational cohort study (N = 24,246) examined the long-term effects of GLP-1 receptor agonists on cardiovascular health in patients with obesity. Patients had a mean age of 43 years with a body mass index of 30 kg/m² or greater and without type 2 diabetes. The study group was 80% female. Patients were from the United States, Australia, Europe, and Asia. All patients experienced an index event (ie, mortality, thyroid disease, cardiovascular event [including stroke], kidney disease) during the 5-year study period.²

The study authors excluded patients taking an additional glucose-lowering medication, those who used the study drugs for less than 6 months, patients who had index events before the study baseline, those using other weight management medications, and those with a history of bariatric surgery, cancer, kidney failure, HIV infection, pancreatitis, or kidney transplant. The intervention was a prescription for GLP-1 receptor agonists for at least 6 consecutive months before any index event. The comparator was a propensity score-matched cohort of patients with no history of GLP-1 receptor agonist use. The primary outcomes were safety and cardiovascular (including stroke), thyroid, and clinical biochemical profile outcomes.²