Incretin-based therapies were associated with a lower risk of dementia compared with sulfonylureas in older adults with type 2 diabetes, highlighting potential cognitive benefits relevant to long-term diabetes management.
In an interview with Pharmacy Times, Christel Renoux, MD, PhD, associate professor in the Department of Neurology and Neurosurgery at McGill University; and Oriana Hoi Yun Yu, MD, MSc, associate professor at McGill University and endocrinologist at Jewish General Hospital, discussed findings from a large observational study evaluating the association between incretin-based therapies and dementia risk in adults 50 years or older with type 2 diabetes. The investigators—who authored
For pharmacists, these findings support a more holistic approach to diabetes management in older adults, where cognitive outcomes are considered alongside glycemic control and cardiometabolic risk.
Pharmacy Times: Can you summarize these findings in practical terms for pharmacists who manage patients on glucose-lowering therapies?
Christel Renoux, MD, PhD; and Oriana Hoi Yun Yu, MSc, MD: We assessed whether DPP-4 inhibitors and GLP-1 receptor agonists reduce the risk of dementia compared with sulfonylureas in a large cohort of adults 50 years or older with type 2 diabetes. We found that DPP-4 inhibitors were associated with a 23% lower risk of dementia compared with sulfonylureas. Results were very similar for GLP-1 receptor agonists, although they did not reach statistical significance. These findings suggest that incretin-based therapies may offer advantages for cognitive health over sulfonylureas, particularly in older adults or those at higher dementia risk.
Pharmacy Times: The analysis suggested that the magnitude of the association with reduced dementia risk increased with longer cumulative exposure to these agents. How should pharmacists interpret this in the context of counseling patients on long-term diabetes therapy?
Renoux and Yu: Indeed, these results suggest that the potential neuroprotective benefits of incretin-based drugs accumulate over time, with longer exposure showing greater benefit. In practice, if these results are confirmed in additional studies, they indicate that these drugs may offer benefits when taken over extended periods and that staying on these medications consistently may help support long-term brain health. Thus, adherence and long-term diabetes management remain important.
Pharmacy Times: GLP-1 receptor agonists showed a similar trend but with greater uncertainty. What do you think explains the difference in confidence between the DPP-4 inhibitor and GLP-1 RA results, and what additional data might we need?
Renoux and Yu: GLP-1 receptor agonists may reduce the risk of dementia, but the results were less precise due to a smaller sample size and fewer events, which limited statistical precision. Still, the direction of effect was consistent with results for DPP-4 inhibitors. Larger cohorts with more GLP-1 receptor agonist users and longer follow-up will be needed to confirm these results and strengthen real-world evidence about the potential cognitive benefits of incretin-based drugs.
Pharmacy Times: How might this research influence the way pharmacists approach medication review and optimization for older adults with type 2 diabetes who are at risk for cognitive decline?
Renoux and Yu: There is increasing focus on brain health and cognitive outcomes alongside glycemic targets and cardiometabolic complications of type 2 diabetes. Therefore, long-term diabetes management and treatment optimization that may also support long-term brain health are important to consider. While additional research is needed on the potential neuroprotective effects of incretin-based drugs, for patients already using these medications, such as GLP-1 receptor agonists for cardiometabolic benefits, potential cognitive benefits may be an additional advantage. Therefore, maintaining long-term adherence when treatment is well tolerated and indicated is important, alongside comprehensive management of other risk factors. In addition, when weighing treatment choices, the possibility of cognitive benefit can be incorporated into conversations with patients about diabetes management and long-term treatment planning.
Pharmacy Times: Are there specific patient populations—such as those with existing cognitive concerns or multiple comorbidities—where you think pharmacists should be particularly attentive to the potential cognitive benefits of DPP-4 inhibitors or GLP-1 receptor agonists?
Renoux and Yu: Patients with type 2 diabetes who have multiple comorbidities, vascular complications, or other factors that contribute to cognitive decline may particularly benefit from specific agents with potential cognitive benefits. Results from this study are encouraging and suggest a possible protective effect of incretin-based drugs, in line with several other population-based studies that point to a decreased risk of dementia, particularly with GLP-1 receptor agonists. Experimental studies also suggest that both DPP-4 inhibitors and GLP-1 receptor agonists have biologically plausible neuroprotective mechanisms (eg, reducing inflammation, oxidative stress, and amyloid burden). In addition, complications associated with diabetes treatments, such as hypoglycemia, can also affect cognitive function. Thus, the lower risk of hypoglycemia associated with incretin-based drugs compared with sulfonylureas may also contribute to a lower risk of cognitive decline.
While these results are promising, more research is needed to fully understand the mechanisms involved and to confirm the effect of these drugs in larger population-based studies with longer follow-up. It will also be valuable to explore these potential benefits in patients prescribed these drugs for weight loss rather than for type 2 diabetes.
