Study: GLP-1, SGLT2s Linked to Reduced Alzheimer Disease Risk in Patients with Type 2 Diabetes
A new study found that patients with type 2 diabetes treated with GLP-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors demonstrated lower risks of developing Alzheimer disease compared to other glucose-lowering drugs.
Image Credit: Adobe Stock Images/sandra
With increasing rates of Alzheimer disease (AD) and related dementias (ADRD), patients with type 2 diabetes (T2D), who face an elevated risk of cognitive decline, represent a critical group for prevention efforts. A recent study conducted by the University of Florida College of Pharmacy and published in JAMA Neurology suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) could potentially prevent the development of ADRD in patients with T2D.
The study authors analyzed electronic health record data from the OneFlorida+ Clinical Research Consortium between January 2014 and June 2023, focusing on patients over 50 years of age with T2D and no prior diagnosis of ADRD. The analysis included 33,858 patients using GLP-1RAs and 34,185 using SGLT2is, compared to other glucose-lowering drugs (GLDs). The study excluded patients who had previously received antidementia treatments. The primary endpoint was the incidence of ADRD, including AD, vascular dementia, frontotemporal dementia, and Lewy body dementia.
The results indicated that patients using GLP-1RAs had a 33% lower risk of developing ADRD, while those on SGLT2is exhibited a 43% lower risk compared to other GLDs. Between the two treatment groups, there was no significant difference in ADRD risk, with the GLP-1RA group demonstrating 2.26 fewer cases per 1,000 person-years compared to the control group and the SGLT2i group showing 3.05 fewer cases per 1,000 person-years compared to the control group.1
“It’s exciting that these diabetes medications may offer additional benefits, such as protecting brain health,” said Serena Jingchuan Guo, MD, PhD, assistant professor, pharmaceutical outcomes and policy, senior author of the study, in a press release. “Based on our research, there is promising potential for GLP-1RAs and SGLT2is to be considered for Alzheimer’s disease prevention in the future. As use of these drugs continues to expand, it becomes increasingly important to understand their real-world benefits and risks across populations.”2
According to the investigators, the study’s strengths included the use of a rigorous methodology compared to traditional observational studies, enhancing the validity of its findings. Additionally, results were consistent across multiple sensitivity and subgroup analyses, reinforcing the reliability of the conclusions. Furthermore, there was extensive adjustment for numerous baseline covariates, reducing potential biases as a result.
The authors of the study also acknowledged several limitations. First, the follow-up period was relatively short, especially for GLDs, which limits the ability to fully assess long-term outcomes related to ADRD. Additionally, the identification of ADRD cases was based on diagnosis codes, which may introduce misclassification or inaccuracies. Lastly, the authors suggested that overall findings may not be applicable to all populations, necessitating further validation in diverse cohorts and contexts.1,2
The authors concluded that the potential neuroprotective effects of GLP-1RAs and SGLT2is highlight their possible incorporation into ADRD prevention strategies. Moving forward, these treatments could offer flexibility in treatment options while potentially providing cognitive benefits. However, additional research is needed to confirm these findings and evaluate their relevance across different populations, with the authors underscoring the necessity of randomized controlled trials.1
“Future research should focus on identifying heterogeneous treatment effects—specifically, determining which patients are most likely to benefit and who may be at greater risk for safety concerns,” Guo said in the press release.2
References
1. GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias. JAMA Neurology. April 7, 2025. Accessed April 17, 2025. https://jamanetwork.com/journals/jamaneurology/article-abstract/2831976
2. Popular diabetes medications, including GLP-1 drugs, may protect against Alzheimer’s disease. EurekAlert! April 16, 2025. Accessed April 17, 2025.
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