A new study links two widely prescribed diabetes drugs to a 33–43% lower risk of Alzheimer’s and related dementias, offering hope for repurposing existing treatments to tackle one of aging’s most devastating diseases.
Study: GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias. Image Credit: PeopleImages.com - Yuri A / Shutterstock.com
A recent study published in the journal JAMA Neurology determines the potential impact of novel anti-diabetes medications on the risk of developing Alzheimer’s dementia and related dementias (ADRD).
Novel approaches for treating ADRD
ADRD, which is characterized by progressive cognitive impairment, currently affects about seven million older adults in the United States, with researchers projecting that up to 14 million people will be diagnosed with ADRD in the U.S. by 2060. Recently, the U.S. Food and Drug Administration (FDA) has approved several disease-modifying treatments for AD, some of which include aducanumab, lecanemab, and donanemab; however, their efficacy and risks remain unclear.
To overcome the high costs and potential adverse effects associated with novel AD drugs, researchers have become increasingly interested in repurposing existing drugs for novel therapeutic indications. For example, several studies have recently reported that glucose-lowering drugs like glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) may reduce the risk of ADRD. Despite these observations, the association between these drugs and ADRD risk remains unclear.
Study findings
Electronic health record data from OneFlorida+ Clinical Research Consortium were obtained between January 2014 to June 2023. All patients were at least 50 years old, diagnosed with T2DM, with no previous diagnosis of ADRD.
Patients who were prescribed either GLP-1RAs or SGLT2is were more likely to be female, younger than the overall mean age of the T2DM cohort, and have higher body mass index (BMI) values as compared to patients prescribed other glucose-lowering drugs.
The incidence of ADRD was lower among patients who were prescribed GLP-1RAs as compared to other anti-diabetes drugs, with an incidence rate of 4.35 and 6.6 for every 1,000 person years, respectively. Patients who were prescribed SGLT2is also had a lower risk of ADRD, at a rate of 4.19 cases for every 1,000 person years as compared to 7.23 cases among patients prescribed other glucose-lowering drugs.
These findings demonstrate that both GLP-1RA and SGLT2 use were associated with a significantly reduced risk of developing ADRD. No significant difference in ADRD risk was observed when comparing GLP-1RA and SGLT2 use.
GLP-1RAs are associated with numerous health benefits that may contribute to the reduced risk of ADRD among diabetics, some of which include reduced neuroinflammation, improved insulin sensitivity in the brain, and greater neurogenesis. These drugs may also promote synaptic plasticity while reducing the accumulation of amyloid-β and tau proteins.
SGLT2is may also increase blood flow to the brain and reduce exposure to oxidizing molecules, while promoting mitochondrial function.
Both drug classes are associated with improved vascular health and beneficial metabolic effects, which are strongly linked to cognitive performance. The mechanisms of action shared between both GLP-1RAs and SGLT2is likely to contribute to their similar risk reduction profile for ADRD.
GLP-1RA use was associated with a 33% lower risk of ADRD, while SGLT2i use was associated with a 43% lower risk as compared to other glucose-lowering drugs.”
Future outlook
The development of ADRD is a protracted process that typically occurs over several years, with pathological changes often emerging before clinical symptoms can be detected. Thus, due to the short follow-up period for the current analysis, additional studies are needed to confirm the long-term neuroprotective effects of both GLP-1RAs and SGLT2is.
Longitudinal studies, particularly randomized controlled trials (RCTs), are needed to monitor the long-term effects of GLP-1RA and SGLT2i use on ADRD risk in diabetics. Additional studies that apply more rigorous analytical methods while also adjusting for covariate factors are also indicated.
Nevertheless, the study findings suggest that GLP-1RAs and SGLT2is have neuroprotective effects that could be used as part of broader therapeutic regimens to prevent ADRD in diabetics. Notably, the reduced ADRD risk remained consistent when diverse ethnicities, sex, obesity status, and the use of insulin or metformin were considered in the analysis, thus suggesting the generalizability of these observations.
Journal reference:
- Tang, H., Donahoo, W. T., DeKosky, S. T., et al. (2025). GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias. JAMA Network. doi:10.1001/jamaneurol.2025.0353.