GLP-1-RAs May Lower Secondary Stroke Risk in Diabetes, Obesity

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) vs placebo reduce secondary stroke risk by 16% in stroke survivors with diabetes or obesity, according to study findings published in the International Journal of Stroke.

Researchers conducted a systematic review and meta-analysis to evaluate the effects of GLP-1RAs (ie, dulglutide, efpeglenatide, albiglutide, exenatide, semaglutide, liraglutide, and lixisenatide) on secondary stroke risk. The researchers searched databases through November 2023 for randomized cardiovascular outcome trials involving adults with or without type 2 diabetes who were randomly assigned to received either GLP-1RAs or placebo. The primary outcome was stroke during follow-up, while secondary outcomes included non-fatal and fatal strokes. Statistical analyses were conducted using RevMan 5.4.1.

A total of 11 randomized clinical trials were included in the meta-analysis, 9 of which involved patients with diabetes mellitus, 1 with obesity, and 1 with heart failure. Prior stroke events were reported in 8 of the 11 trials. The follow-up period ranged from 5.7 to 66 months and totaled 247,596 person-years.

In all, the 11 studies comprised 82,140 patients (women, 34.6%; diabetes mellitus, 78.4%; heart failure, 18.7%; history of stroke, 16.7%), 41,726 (50.8%) of whom were randomly assigned to receive GLP-1RAs and 40,414 (49.2%) of whom received placebo.

Nine of the studies, which comprised 60,380 patients, assessed the primary outcome. Among these patients, 770 strokes (2.5%) occurred in the GLP-1RA group (n=30,848) and 883 strokes (3%) occurred in the placebo group (n=29,532). A significantly lower rate of stroke was exhibited by the GLP-1RA vs placebo group (risk ratio [RR], 0.85; 95% CI, 0.77-0.93).

Ten studies, which comprised 81,840 patients, evaluated the secondary outcome of non-fatal stroke. Among these patients, 848 non-fatal strokes (2%) occurred in the GLP-1RA group (n=41,572) and 954 (2.4%) occurred in the placebo group (n=40,268). Again, the GLP-1RA vs placebo group demonstrated a significantly lower rate of non-fatal strokes (RR, 0.87; 95% CI, 0.79-0.95).

The secondary outcome of fatal stroke was assessed in 8 trials comprising 60,080 patients. A total of 100 fatal strokes (0.3%) occurred in the GLP-1RA group (n=30,694) and 118 fatal strokes (0.4%) occurred in the placebo group. Between the 2 groups, no significant difference in the risk for fatal strokes was observed (RR, 0.81; 95% CI, 0.62–1.06; P =.75).

Study limitations included the lack of individual patient data, small sample of patients with a history of stroke, inclusion of 7 different GLP-1 RAs, and lack of safety outcome data. “This finding may increase implementation of GLP-1 RAs by stroke specialists in individuals with stroke and comorbid diabetes mellitus or obesity,” the researchers concluded.

Disclosure: Several study authors declared affiliations with biotech and pharmaceutical companies. Please see the original reference for a full list of author