Weight loss Drugs May Reduce Alzheimer’s Risk in People With Type 2 Diabetes

A recent study published in JAMA Neurology, indicates that commonly prescribed medications for diabetes and weight management including Ozempic, Wegovy, and Mounjaro, may also help protect against Alzheimer’s disease. Researchers studied nearly 400,000 adults over age 50 with type 2 diabetes and found that GLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2is) linked to a lower risk of developing Alzheimer’s disease.

GLP-1RAs and SGLT2is Linked to Reduced ADRD Risk by 33% and 43% Respectively

The University of Florida conducted a multi-cohort study that found GLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2is) linked to a significantly lower risk of Alzheimer’s disease and related dementias (ADRD) compared to other diabetes medications.

Analyzing data from over 90,000 patients, researchers reported that GLP-1RA users had a 33% lower risk and SGLT2i users had a 43% lower risk of developing ADRD. Although SGLT2is showed a slightly greater reduction, the difference between the two drug classes was not statistically significant, suggesting both may provide comparable protective benefits.

Additional findings from a separate study led by the University of Galway support the potential of GLP-1 receptor agonists in lowering dementia risk. Through a systematic review and meta-analysis of 26 randomized clinical trials involving more than 164,000 participants, researchers identified a statistically significant link between GLP-1RA use and reduced dementia incidence.

In contrast to the Florida study, the analysis from the University of Galway did not observe similar cognitive benefits associated with SGLT2 inhibitors or pioglitazone. These results indicate that GLP-1 receptor agonists may play a more specific role in supporting cognitive function compared to other cardioprotective diabetes treatments.

Dementia Affects Nearly 7 Million in the U.S. and Could Double by 2060

Dementia, including Alzheimer’s disease and related conditions, is among the fastest-growing public health concerns. It currently affects nearly 7 million people in the United States, a number expected to double by 2060. Although newly approved Alzheimer’s treatments such as lecanemab and aducanumab have drawn attention, ongoing concerns about their safety and effectiveness have increased interest in repurposing widely used, well-tolerated medications.

Researchers initially developed GLP-1 receptor agonists, such as semaglutide, to stimulate insulin secretion, reduce blood sugar levels, and promote weight loss in individuals with type 2 diabetes.

Subsequent research has identified GLP-1 receptors in various parts of the body beyond the pancreas and gastrointestinal tract, including the brain, heart, and immune system. In animal studies, GLP-1RAs have demonstrated the ability to reduce brain inflammation, improve synaptic plasticity, and lower the buildup of amyloid-β and tau proteins, hallmarks of Alzheimer’s disease.

In an editorial published in JAMA Neurology, Dr. Diana Thiara from the University of California, San Francisco, calls the brain effects of newer agents like semaglutide “highly promising,” noting their stronger and longer-lasting receptor activity. She adds, “We are only at the precipice,” highlighting ongoing trials of dual and triple hormone agonists that could offer even greater neuroprotective benefits in the future.

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Author

Denisse Sandoval