GLP-1 RAs may lower long-term mortality risk in AIS patients

The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) appears to contribute to a long-term reduced risk of death in patients with acute ischaemic stroke (AIS), suggests a study. However, less than 1 percent of these individuals have been prescribed GLP-1 RAs upon discharge.

“In a large, contemporary cohort of patients with AIS, only 0.5 percent were prescribed GLP-1 RAs at or shortly after discharge, although prescription rates increased over time,” said lead study author Dr Marialaura Simonetto, Weill Cornell University, New York, New York, US, who presented the findings at the recent ISC 2026.

Simonetto and her team conducted a retrospective cohort study using data from TriNetX to “investigate temporal trends in GLP-1 RA prescriptions after AIS and to study the association between GLP-1 RAs ... and long-term mortality.”

TriNetX is a global, real-world clinical dataset derived from electronic health record (EHR) systems and linked to claims/mortality sources. Simonetto and colleagues obtained EHR, pharmacy, and insurance claims data from 2016 to 2023 on over 11 million patients at 29 healthcare organizations across the US. Those with an index hospitalization for AIS using validated ICD-10-CM codes were included in the study. 

The authors then calculated crude rates of GLP-1 RA prescription 90 days after discharge. They also explored the association between GLP-1 RA prescription, modelled as a time-varying covariate, and long-term mortality using Cox proportional hazard models, with adjustments for demographic and cardiovascular comorbidities.

Overall, 56,801 patients (mean age 59 years, 47 percent women, 55 percent White) were discharged after AIS. Of these, only 298 (0.5 percent) were prescribed a GLP-1 RA within 90 days after discharge. [ISC 2026, abstract A075]

A subgroup consisting of 34,156 (60 percent) AIS patients had either diabetes or BMI ≥27 kg/m². Of these, only 290 (0.85 percent) were prescribed GLP-1 RAs.

Simonetto noted that stroke survivors with a GLP-1 RA prescription tended to be younger, more often had commercial insurance, had a higher median BMI, and a higher prevalence of hypertension and diabetes relative to those who did not receive a prescription.

Notably, GLP-1 RA prescription within 90 days after discharge showed an increasing trend over the years. In 2016, the crude rate of such prescriptions was 0.24 percent, and this significantly rose to 0.75 percent in 2023 (odds ratio per year, 1.20, 95 percent confidence interval [CI], 1.13–1.27).

Survival benefit

Furthermore, adjusted Cox models demonstrated the survival benefits derived from GLP-1 RAs. AIS patients prescribed a GLP-1 RA exhibited a significantly lower risk of long-term mortality than those who did not have a prescription (hazard ratio, 0.73, 95 percent CI, 0.53–1.00; p=0.047) during a median follow-up period of 1.4 years.

“GLP-1 RAs were associated with a long-term decreased risk of mortality after AIS,” Simonetto said.

This study, however, had several limitations, including errors in misclassification given the use of ICD-10-CM codes, lack of information on AIS severity that might have influenced prescription rates and mortality, absence of data on aetiologic mechanism of ischaemic stroke, younger population, and prevalently commercial insurance.

Moreover, Simonetto and her team “did not have data on resumptions of antithrombotic or lipid-lowering medication use after AIS, which may have also influenced mortality.”

“GLP-1 RAs have recently been shown to reduce major adverse cardiovascular events in patients with diabetes, obesity, or overweight with prior cardiovascular events,” Simonetta said. “Limited data exists on rates of GLP-1 RA use in patients with AIS and associations with stroke outcomes.”