Research News

Diabetes is a major risk factor for Alzheimer’s disease, but controlling blood sugar alone doesn’t prevent neurodegeneration. Cleveland Clinic researchers analyzed two decades worth of patient data and uncovered a promising connection between certain diabetes medications, including weight loss drugs, and Alzheimer’s disease outcomes.   

The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, analyzed publicly available data from 400,000 individuals who took antidiabetic medications between 2007 and 2025. Prescribing an antidiabetic medication requires an individualized approach. This can include whether a patient needs to lose weight, what other conditions the patient may have, cost and side effects. The research team, co-led by Feixiong Cheng, PhD, Director of Cleveland Clinic’s Genome Center, analyzed multiple types of antidiabetic drugs to add another factor: long-term neuroprotection. 

The Cheng Lab examined three classes of antidiabetic medication for their neuroprotective effects: GLP-1 receptor agonists, including semaglutide and liraglutide; SGLT2 inhibitors, including dapagliflozin, canagliflozin and empagliflozin; and DPP-4 inhibitors (gliptins).  

“Although antidiabetic drugs all help manage blood sugar, they work through different biological pathways,” Dr. Cheng explains. “We wanted to know if some of these medications could also target mechanisms directly linked to the brain and neurodegeneration, and we wanted to know whether individuals with diabetes would need to change from their optimal medication to protect their neurological health.” 

The team analyzed a database of 80 million older (>60 years) patients to see whether any of these medications were associated with lower rates of Alzheimer’s diagnoses. Almost half a million were included in the study.

The findings showed that individuals who took a GLP-1 agonist or SGLT2 inhibitor made 25% - 50% fewer insurance claims related to neurodegenerative disease than individuals who took DPP-4 inhibitors to control their diabetes. There was no significant difference between GLP-1 receptor agonists and SGLT-2 inhibitors. 

"When it comes to GLP-1 RAs, we also found that semaglutide was associated with a ~30-50% reduced risk of Alzheimer's disease in obese individuals, but wasn't significant in people with a normal body mass index,” Dr. Cheng says. “Whether semaglutide has clinical efficacy in individuals with normal weight is still being studied.” 

The results provide preliminary evidence for further studies to validate the neuroprotective benefits of GLP-1 RAs and SGLT-2 inhibitors, and, after validation, to untangle the mechanisms of how GLP-1 drugs may help protect the brain.  

“It’s crucial to investigate whether GLP-1 receptor agonists and SGLT-2 inhibitors could serve as disease-modifying therapies for Alzheimer’s disease in humans by targeting the disease’s biology directly, beyond the drugs’ known anti-diabetic effects,” Dr. Cheng says. “Clinical trials testing these medications are also underway based on the 2025 Alzheimer’s Disease Drug Development Pipeline, but we hope our findings will help direct more targeted, thoughtful clinical trials in the future."