Glucose-lowering drugs may have protective effects against the development of Alzheimer’s disease

A study led by researchers in the University of Florida College of Pharmacy has found that a pair of popular glucose-lowering drugs (GLDs) may have protective effects against the development of Alzheimer’s disease and related dementias (ADRD) in patients with T2DM.

The researchers studied Medicare claims data of older adults with T2DM to assess the association among glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is) and the risk of Alzheimer’s disease and related dementias. The research is supported by funding from the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases, both part of the National Institutes of Health.

This target trial emulation study used electronic health record data from OneFlorida+ Clinical Research Consortium from January 2014 to June 2023. Patients were 50 years or older with T2D and no prior diagnosis of ADRD or antidementia treatment. Among the 396,963 eligible patients with T2D, 33,858 were included in the GLP-1RA vs other glucose-lowering drug (GLD) cohort, 34,185 in the SGLT2i vs other GLD cohort and 24,117 in the GLP-1RA vs SGLT2i cohort.

The researchers found that the incidence rate of ADRD was lower in GLP-1RA initiators compared with other GLD initiators (rate difference [RD], −2.26 per 1000 person-years [95% CI, −2.88 to −1.64]), yielding an HR of 0.67 (95% CI, 0.47-0.96). SGLT2i initiators had a lower incidence than other GLD initiators (RD, −3.05 per 1000 person-years [95% CI, −3.68 to −2.42]), yielding an HR of 0.57 (95% CI, 0.43-0.75). There was no difference between GLP-1RAs and SGLT2is, with an RD of −0.09 per 1000 person-years (95% CI, −0.80 to 0.63) and an HR of 0.97 (95% CI, 0.72-1.32).

The data showed a statistically significant association between a lower risk of Alzheimer’s and the use of GLP-1RAs and SGLT2is compared with other glucose-lowering medications. According to the researchers, the findings indicated that the two drugs may have neuroprotective effects for people without diabetes and may help slow the rate of cognitive decline in Alzheimer’s patients.

Dr Serena Jingchuan Guo, an assistant professor of pharmaceutical outcomes and policy and the study’s senior author, said these findings may point to new therapeutic uses for drugs commonly used to treat Type 2 diabetes and obesity.

“It’s exciting that these diabetes medications may offer additional benefits, such as protecting brain health,” Guo said. “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.”

As the study only included patients with T2DM, Guo said next steps include evaluating the effects of the two drugs in broader populations by using recent, real-world data that captures their growing use in clinical settings.

“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 added.

The findings were featured in the paper, ‘GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias’, published in JAMA Neurology. To access this paper, please click here (log-in maybe required)