Drugs originally developed for type 2 diabetes, particularly GLP-1 receptor agonists (GLP-1RAs) like semaglutide (sold as Ozempic and Wegovy), are now being studied for their potential to protect brain health. Two recent studies and an editorial in JAMA Neurology suggest that these medications may help reduce the risk of dementia, including Alzheimer’s disease.
Dementia, including Alzheimer’s and related disorders, is a rapidly growing public health concern. Currently, nearly 7 million Americans are affected, and this number is expected to double by 2060. While newly approved Alzheimer’s drugs like lecanemab and aducanumab have attracted attention, questions about their effectiveness and safety persist. This has led to increased interest in repurposing existing, widely used medications that are already well-tolerated.
One study conducted by the University of Florida found that GLP-1RAs, as well as SGLT2 inhibitors (SGLT2is), were linked to a significantly lower risk of Alzheimer’s and related dementias (ADRD) when compared to other diabetes medications. The research, which analyzed data from over 90,000 patients, revealed that users of GLP-1RAs had a 33% lower risk, while those on SGLT2 inhibitors had a 43% lower risk of developing ADRD. Though SGLT2 inhibitors showed a slightly greater reduction in risk, the difference between the two drug classes was not statistically significant, indicating that both might provide similar benefits.
A second study, led by researchers at the University of Galway, also suggests that GLP-1 receptor agonists may help lower dementia risk. In a review of 26 randomized clinical trials involving over 164,000 participants, researchers found a statistically significant association between GLP-1RAs and a reduced risk of dementia. Unlike the Florida study, this analysis did not find similar benefits for SGLT2 inhibitors or pioglitazone, indicating that GLP-1RAs may have a more unique role in protecting cognitive function compared to other diabetes medications.
Originally developed to increase insulin secretion, lower blood sugar, and aid weight loss in type 2 diabetes patients, GLP-1 receptor agonists like semaglutide are now also being studied for their effects on the brain. Researchers have found that GLP-1 receptors are present not only in the pancreas and gastrointestinal tract, but also in the brain, heart, and immune system. In animal studies, GLP-1RAs have been shown to reduce brain inflammation, improve synaptic plasticity, and decrease the buildup of amyloid-β and tau proteins, which are hallmarks of Alzheimer’s disease.
In an editorial in JAMA Neurology, Dr. Diana Thiara of the University of California, San Francisco, called these brain effects “highly promising,” particularly with newer GLP-1RAs like semaglutide, which have stronger and longer-lasting effects on the receptors. She also noted that ongoing trials of dual and triple hormone agonists could potentially offer even greater neuroprotective benefits in the future.
Currently, major Phase III clinical trials, including EVOKE and EVOKE Plus, are assessing the effects of semaglutide in individuals with early-stage Alzheimer’s. If the findings confirm these benefits, it could change how clinicians address both diabetes and dementia, especially in older populations where these conditions often overlap.
Despite their promise, GLP-1 receptor agonists are not without risks. Common side effects include nausea, vomiting, and loss of lean muscle mass, which may be a concern for older adults already at risk for sarcopenia. In rare cases, patients may experience pancreatitis, and preclinical studies have raised concerns about a potential risk of thyroid cancer, though this has not been observed in humans.
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