Ozempic and GLP-1 Receptor Agonists May Protect Against Dementia

Medicines that lower blood glucose to manage diabetes, including Ozempic, are continuing to reveal further potential advantages. Protection against dementia could soon join that list.

GLP-1 receptor agonists and dementia risk

GLP-1 receptor agonists are a group of glucose-lowering medicines that have delivered substantial improvements in heart and kidney health during clinical trials. Emerging research now indicates that they may also lower the risk of dementia.

That possibility is particularly encouraging given that an estimated 6.9 million adults in the United States currently live with Alzheimer's and related dementias – a total projected to more than double by 2060.

Diabetes is already recognised as a dementia risk factor. People with diabetes also have a greater likelihood of experiencing strokes caused by blood clots in the brain, which can sometimes lead to vascular dementia.

"But whether glucose-lowering therapies can help prevent cognitive decline has remained unclear," says Catriona Reddin, a medical researcher from the University of Galway. "Our findings suggest that GLP-1 receptor agonists, in particular, may have a protective effect on brain health."

Two studies of glucose-lowering therapies

The research involving Reddin was headed by University of Galway medical students Allie Seminer and Alfredi Mulihano. Meanwhile, a separate study by researchers at the University of Florida was led by epidemiologist Huilin Tang.

Both research groups examined the association between cardiovascular-beneficial glucose-lowering medicines, including GLP-1 agonists and SGLT2 inhibitors, and the risk of cognitive impairment and dementia in people with type 2 diabetes.

Seminer's group reviewed findings from 26 randomised clinical trials, covering more than 160,000 participants. These trials compared dementia diagnoses or cognitive scores between people taking glucose-lowering treatments and those who were not.

The researchers reported that people using GLP-1RAs had a 45 percent lower risk of all-cause dementia and cognitive impairment. The same result was not seen among people taking SGLT2is.

However, when the researchers examined individual dementia types more closely, neither therapy was linked with reduced vascular dementia, Alzheimer disease, or Lewy body dementia.

"This is surprising because we would expect first-line cardioprotective glucose-lowering therapies, like GLP1-RAs and SGLT2is, which reduce cardiovascular dis- ease risk, to also decrease the risk of vascular dementia," University of California San Francisco medical doctor Diana Thiara writes in an editorial published alongside the papers.

Alzheimer's and related dementias findings

Tang's study used a target trial emulation based on records from 396,963 patients with type 2 diabetes. The team assessed the risk of Alzheimer's and related dementias by comparing people who used GLP-1RAs with those taking SGLT2is or other forms of glucose-lowering treatment.

This analysis identified statistically significant reductions in the risk of Alzheimer's disease and related dementias for people using cardioprotective glucose-lowering therapies, whether they took GLP-1RAs or SGLT2is. Other types of glucose-lowering therapy did not show this effect.

"These results support the potential neuroprotections of GLP-1RAs and SGLT2is and highlight their possible role in Alzheimer's and related dementia prevention strategies," Tang and team write.

Thiara notes that both papers had limitations, including brief follow-up periods, low dementia rates, confounding factors that can complicate observational research, and broad classifications of medicines that may include different active ingredients.

"With the advent of more potent GLP-1RAs, like semaglutide, it is crucial to study these newer medications individually rather than grouping them with older drugs in the same class, as their effects may differ significantly," she notes.

The papers are published in JAMA Neurology, here and here.