GLP-1 RAs Protective Against Stroke, Neurodegeneration?

TOPLINE:

Use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), particularly semaglutide and tirzepatide, was associated with a 37% reduced risk for dementia and a 19% reduced risk for ischemic stroke in adults with type 2 diabetes (T2D) and obesity compared to the use of other antidiabetic drugs in a new retrospective cohort study. The neuroprotective effects of GLP-1 RAs were more pronounced in older adults, women, and those with a BMI of 30-40.

METHODOLOGY:

• Investigators analyzed data on more than 60,000 adults aged 40 years or older with T2D and obesity and without type 1 diabetes or preexisting neurodegenerative or cerebrovascular diseases, obtained from electronic health records between 2017 and 2024.
• After propensity-score matching, participants receiving semaglutide or tirzepatide were assigned to the GLP-1 RA group (n = 30,430; mean age, 58 years; 50% women; 56% White individuals), and those receiving biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, and SGLT2 inhibitors were assigned to the “other antidiabetic drug” group (n = 30,430; mean age, 58 years; 51% women; 56% White individuals).
• Primary outcomes were the incidence of new‐onset neurodegenerative diseases (dementia, Parkinson’s disease, and mild cognitive impairment) and cerebrovascular diseases (ischemic stroke and intracerebral hemorrhage). The secondary outcome was all-cause mortality.

TAKEAWAY:

• Patients taking GLP-1 RAs had a significantly lower risk for dementia (hazard ratio [HR], 0.63), ischemic stroke (HR, 0.81), and all-cause mortality (HR, 0.70) than those taking other antidiabetic drugs.
• Compared with use of other antidiabetic drugs, use of semaglutide was associated with reduced risk for dementia (HR, 0.63), whereas use of tirzepatide was associated with reduced risk for stroke (HR, 0.69) and all-cause mortality (HR, 0.48).
• No significant differences in risk for Parkinson’s disease or intracerebral hemorrhage were observed between the GLP-1 RA group and the other antidiabetic group.
• The neuroprotective effects of GLP-1 RAs were more pronounced in women (HR, 0.85), adults aged 60 years or older (HR, 0.85), White individuals (HR, 0.86), and those with a BMI of 30-40 (HR, 0.82).

IN PRACTICE:

“These findings suggest that semaglutide and tirzepatide may offer neuroprotective and cerebrovascular benefits beyond glycemic control, potentially improving long-term cognitive and survival outcomes in adults with T2D and obesity,” the investigators wrote.

“If shown to be protective for neurodegenerative diseases in future trials, GLP-1 RAs could potentially be used clinically in disease prevention in the future,” Sarah Marzi, PhD, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, England, said in an online comment. Marzi was not involved with the current research. 

SOURCE:

The study was led by Huan-Tang Lin, MD, PhD, Chang Gung Memorial Hospital, Taoyuan, Taiwan. It was published online on July 15 in JAMA Network Open.

LIMITATIONS:

As an observational study, residual confounding from unmeasured factors such as frailty or functional status could not be excluded, potentially introducing healthy user or selection bias. The database used lacked biomarker data, genetic profiles, and neuroimaging assessments, limiting further mechanistic interpretations. The analysis did not account for death as a competing risk. Additionally, medication exposure was inferred from prescriptions without confirmation of actual adherence or accurate drug doses.

DISCLOSURES:

The study was funded by the Ministry of Science and Technology, Taiwan, and the Chang Gung Memorial Hospital. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.