Incretin-based diabetes drugs show potential protective effects against dementia

A large McGill University study has found that two classes of medications commonly prescribed for Type 2 diabetes, both incretin-based, are associated with a reduced risk of dementia.

Drawing on clinical data from more than 450,000 patients, the research adds to growing evidence that incretin-based therapies have protective benefits for the brain.

The study examined GLP-1 receptor agonists, which include such medications as Ozempic, as well as DPP-4 inhibitors.

These are very promising results. By measuring factors that were unaccounted for in earlier studies, our results provide more reliable evidence of the potential cognitive benefits."

Dr. Christel Renoux, associate professor in McGill's Department of Neurology and Neurosurgery and senior investigator at the Lady Davis Institute

Type 2 diabetes increases the risk of dementia by about 60 per cent, and there are few known strategies for reducing the risk, she added. The number of Canadians living with dementia is projected to reach one million by 2030.

Stronger associations with longer use

For about three years, researchers followed patients age 50 or older who were starting the incretin-based therapies and those taking another common diabetes medication, sulfonylureas.

DPP-4 inhibitors were associated with a 23-per-cent lower dementia risk compared with sulfonylureas, which served as a comparison group and are not known to offer cognitive protection. The longer people used the DPP-4 inhibitors, and the higher the dose, the stronger the association became. GLP-1 receptor agonists showed a similar pattern, though with less certainty because fewer patients were using these newer medications.

"While there has been enormous attention on GLP-1 drugs, these findings suggest DPP-4 inhibitors also deserve a closer look," said Renoux.

Study designed to reduce bias

Earlier studies have pointed to cognitive benefits of incretin-based therapies, but many lacked detailed information on patient health, including the severity of diabetes, a major predictor of dementia on its own. Using richer clinical data from the U.K.'s Clinical Practice Research Datalink, the authors were able to control for these and other factors, yielding a more reliable comparison.

"These results give us solid evidence for something scientists have suspected for some time," said Renoux. "These drugs may have benefits far beyond blood-sugar control that we are only beginning to understand."

She noted that longer-term studies will be needed to confirm the results, including in people now using GLP-1 drugs for weight loss.