Medications designed to treat diabetes by lowering blood sugar levels, like Ozempic, continue to turn up added benefits, and protection from dementia may soon be added to the list.
GLP-1 receptor agonists are a particular class of glucose-lowering drugs that can significantly improve heart and kidney health in clinical trials, and recent studies suggest they could also reduce dementia risk.
That’s an appealing prospect when an estimated 6.9 million US adults are living with Alzheimer’s and related dementias today – a number that is expected to more than double by 2060.
We already know diabetes is a risk factor for dementia, and that people with diabetes are more likely to experience strokes from blood clots in the brain, which are known to sometimes result in 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.”
The study Reddin worked on was led by University of Galway medical students Allie Seminer and Alfredi Mulihano. A second, separate study from a University of Florida team was led by epidemiologist Huilin Tang.
Both teams studied how glucose-lowering drugs with cardiovascular benefits, like GLP-1 agonists and SGLT2 inhibitors, were associated with risk of cognitive impairment and dementia, specifically in people with type 2 diabetes.
Seminer’s team analyzed the results of 26 randomized clinical trials, equating to more than 160,000 participants, which compared dementia diagnoses or cognitive scores among people who took glucose-lowering therapies, and those who didn’t.
They found people who used GLP-1RAs had a 45 percent lower risk of all-cause dementia and cognitive impairment, though this was not the case for those using SGLT2is.
But on closer inspection of dementia subtypes, these therapies had no association with lowering 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.
The second study, led by Tang, was a target trial emulation using records from 396,963 patients with type 2 diabetes. The researchers analyzed the risk of Alzheimer’s and related dementias, comparing results for people who used GLP-1RAs and those taking SGLT2is or other kinds of glucose-lowering therapies.
This study found statistically significant risk reductions in Alzheimer’s disease and related dementias among people who used cardioprotective glucose-lowering therapies, regardless of whether they were GLP-1RAs or SGLT2is. This was not the case for other kinds of glucose-lowering therapies.
“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 points out that both papers were limited by short follow-up durations, low dementia rates, confounding factors that muddy observational studies, and the broad strokes taken in classifying these drugs, which may contain 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.
