A large McGill University study found that two classes of drugs commonly prescribed for Type 2 diabetes, both incretin-based, were associated with a reduced risk of dementia.
Based 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 looked at GLP-1 receptor agonists, which include drugs such as Ozempic, as well as DPP-4 inhibitors.
“These are very promising results,” said Dr. Christel Renoux, associate professor in McGill’s Department of Neurology and Neurosurgery and senior researcher at the Lady Davis Institute. “By measuring factors not captured in previous studies, our results provide more reliable evidence of potential cognitive benefits.”
Type 2 diabetes increases the risk of dementia by about 60 percent, and there are few known strategies to reduce the risk, he added. The number of Canadians living with dementia is projected to reach one million by 2030.
Stronger associations with more use
For about three years, researchers followed patients age 50 and older who were starting incretin-based therapies and those taking another common diabetes drug, sulfonylureas.
DPP-4 inhibitors were associated with a 23 percent lower risk of dementia compared to sulfonylureas, which served as a comparison group and are not known to offer cognitive protection. The longer people used DPP-4 inhibitors and the higher the dose, the stronger the association became. GLP-1 receptor agonists showed a similar pattern, although with less certainty because fewer patients were using these newer drugs.
“While enormous attention has been paid to GLP-1 drugs, these findings suggest that DPP-4 inhibitors also deserve a closer look,” said Renoux.
Study designed to reduce bias
Previous studies have pointed to the cognitive benefits of incretin-based therapies, but many lacked detailed information about the patients’ health, including the severity of diabetes, a major predictor of dementia itself. Using richer clinical data from the UK Clinical Practice Research Association, the authors were able to control for these and other factors, giving a more reliable comparison.
“These results give us solid evidence for something that scientists have suspected for some time,” Renoux said. “These drugs may have benefits far beyond blood sugar control that we are just beginning to understand.”
He noted that longer-term studies will be needed to confirm the results, including in people now using GLP-1 drugs for weight loss.
