GLP-1 Receptor Agonists Could Reduce Stroke Risk in Type 2 Diabetes

Rushad Patell, MD
Credit: BIDMC

New data from a study of more than 650,000 patients with type 2 diabetes suggests use of GLP-1 receptor agonists (GLP-1 RA), like semaglutide, could reduce stroke risk.

The propensity-score matched analysis, which was presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, compared the effects of GLP-1 RA use relative to DPP-4 inhibitor, another antihyperglycemic agent, and concluded use of GLP-1 RAs was associated with an 18% reduction in risk of venous thromboembolism.

“Our study showed that the use of a GLP-1 receptor agonist is associated with lower incidence of VTE over one year,” said lead investigator Rushad Patell, MD, assistant professor of medicine at Harvard Medical School in Boston. “If you’re selecting an antidiabetic agent for a patient and thrombotic risk comes into play, this data suggests that there may be some advantage to choosing a GLP-1 receptor agonist.”

Although GLP-1 RAs have gained notoriety in recent years as a result of revelations surrounding their weight loss potential in populations with overweight and obesity, the class has had a home in management of type 2 diabetes dating back to 2005, with the US FDA approval of exenatide.At the start of 2024, 4 different GLP-1 RAs boasted approvals in type 2 diabetes, not including the dual GIP/GLP-1 receptor agonist tirzepatide.

Prior to the paradigm-shifting 2021 approval of semaglutide 2.4 mg for chronic weight management, information elucidating cardiorenal protective benefits of GLP-1 RA contributed to a role as a foundational therapy in management ion glycemic control for millions with type 2 diabetes since the initial approval of exenatide in 2005.

The study from ASH 2024 was launched by Patell and an international team representing institutions in the US, Europe, and Asia to further explore the potential cardiovascular benefit of GLP-1 RAs beyond atherosclerotic cardiovascular disease. Investigators designed their study as a retrospective, propensity score-matched multicenter database analysis and leveraged the TriNetX Analytics Network as a data source.

Patients were matched based on predetermined clinical variables, including age, sex, race, BMI, hemoglobin A1c, use of other anti-diabetic agents including metformin and insulin, and underlying comorbidities based on the components of the Charleston Comorbidity index. The primary outcome of interest for the study was the incidence rate per 1000-patient years of all VTE at 1-year after the index date of first initiation of GLP1-RA or DPP-4 inhibitors.

Excluding those with a history of use of oral anticoagulation, prior VTE, or atrial fibrillation, investigators identified 656,588 eligible patients, including 366,369 receiving GLP-1 RAs and 290,219 receiving DPP-4 inhibitors. After propensity score matching, investigators identified 168,428 patients who received GLP1-RA and DPP-4 inhibitors, respectively, for inclusion in their final analysis.

Result of the analysis suggested the incidence of VTE was 11.0 events per 1000 patient-years among those receiving GLP-1 RAs compared to 12.9 among the DPP-4 inhibitor cohort (Hazard ratio [HR], 0.82; 95% Confidence Interval [CI], 0.77 to 0.88). Secondary analysis revealed those receiving GLP-1 RAs had a reduced risk of both pulmonary embolism (HR, 0.78; 95% CI, 0.71 to 0.86) and deep vein thrombosis (HR, 0.85; 95% CI, 0.79 to 0.92) relative to their counterparts receiving DPP-4 inhibitors.

Additionally, investigators called attention to a subgroup analysis suggesting a similar benefit from GLP-1 RA use on VTE was achieved in patients with obesity (HR, 0.80 [95% CI: 0.73-0.89) and without obesity (HR, 0.82; 95% CI, 0.71 to 0.96).

“From a public health perspective, given how prevalent these drugs are, there is potential to see if the overall burden of VTE might be reduced at a national or population level,” Patell added. “VTE risk seems to continuously go up; maybe this will bring the curve down.”

References:

Chiang CH, Osataphan S, Chang Y, et al. Glucagon-like Peptide 1 Receptor Agonists Reduce the Risk of Venous Thromboembolism in Patients with Diabetes Irrespective of Obesity: A Propensity Score-Matched Multicenter Database Analysis. Presented at: 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10; San Diego, California.

American Society of Hematology. Research shows how lifestyle factors and diet affect hematologic care. Hematology.org. December 7, 2024. Accessed December 8, 2024. https://www.hematology.org/newsroom/press-releases/2024/research-shows-how-lifestyle-factors-and-diet-affect-hematologic-care.

Campbell P. Semaglutide: The drug of today and a steppingstone to Tomorrow. HCP Live. December 6, 2023. Accessed December 8, 2024. https://www.hcplive.com/view/semaglutide-drug-today-steppingstone-tomorrow.