Type 2 Diabetes Drugs Cut Dementia Risk

People taking a little-known class of diabetes drugs are developing dementia at notably lower rates than those on older medications. The finding, from a study tracking over 450,000 patients with Type 2 diabetes, suggests that DPP-4 inhibitors – pills most people have never heard of – might be doing something unexpected: protecting the brain whilst managing blood sugar.

The effect isn’t subtle. Among roughly 275,000 patients, those taking DPP-4 inhibitors developed dementia 23 per cent less often than people taking sulfonylureas, an older drug class. And the protection seemed to strengthen with longer use and higher doses.

“These are very promising results,” says Christel Renoux, who led the research at McGill University in Montreal. Type 2 diabetes raises dementia risk by about 60 per cent, and there are few known ways to reduce that risk. If medications people are already taking for their blood sugar could simultaneously shield their minds, that matters.

It’s a curious moment in the story of diabetes drugs. We’ve spent years obsessing over GLP-1 receptor agonists – the medications everyone now knows as Ozempic and Wegovy – largely because they’re remarkably good at helping people lose weight. But Renoux’s team found that DPP-4 inhibitors, their less glamorous cousins, might offer something equally valuable: a way to keep our cognitive function intact as we age.

Both drug classes work through incretins, hormones that help regulate blood sugar. GLP-1 drugs mimic these hormones directly; DPP-4 inhibitors stop the body breaking them down. Until recently, most researchers assumed their benefits ended with metabolism. That assumption looks increasingly questionable.

The McGill study, published in Drug Safety, is the largest to examine this question. Crucially, Renoux’s team managed to sidestep pitfalls that had undermined earlier research. Previous studies hadn’t properly accounted for diabetes severity – a significant problem, since people with worse diabetes face higher dementia risk regardless of which treatment they receive. Using detailed clinical records from UK general practices, the researchers could control for these factors.

The results held across different types of dementia – Alzheimer’s, vascular dementia, and others. They held across individual DPP-4 molecules (there are several on the market). Among the DPP-4 group, dementia developed at 4.4 cases per 1,000 person-years, compared with 5.7 in the comparison group.

GLP-1 drugs showed a similar pattern, though with considerably more uncertainty. Fewer patients were using these newer medications, which makes the statistics wobblier. Among about 181,000 people starting GLP-1 drugs, dementia rates dropped from 3.1 to 2.3 per 1,000 person-years. The confidence intervals are wide enough that chance could explain the result, but the dose-response relationship – more drug, less dementia – hints at something genuine.

“While there has been enormous attention on GLP-1 drugs, these findings suggest DPP-4 inhibitors also deserve a closer look,” Renoux says. Fair point. The drugs are cheaper, easier to take (they’re pills rather than injections), and have been prescribed for longer. If they’re genuinely protecting brains, that’s worth knowing.

How might they work? Incretin hormones bind to receptors throughout the body, including in the brain, where they could reduce inflammation, improve blood flow, or protect neurons directly. Or perhaps better blood sugar control itself shields the brain – though if that were the complete story, you’d expect all diabetes drugs to show similar effects. They don’t.

Caveats exist, naturally. The study followed people for roughly three years on average; dementia typically takes decades to develop, so any cognitive benefits would need time to become fully apparent. The researchers couldn’t account for every possible confounding factor – adherence to treatment, for instance, or subtle differences in how doctors prescribe these medications to different patients.

And we’re still learning about long-term effects of GLP-1 drugs in people taking them primarily for weight loss rather than diabetes. Do the same protective effects hold in that population? We don’t yet know. Longer studies will be needed.

Still, with Canada expecting a million people living with dementia by 2030, and few proven strategies to reduce risk, the finding carries weight. Type 2 diabetes affects hundreds of millions worldwide. If medications they’re already taking could simultaneously protect their brains, that represents a remarkable convergence – treating one condition whilst preventing another.

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

The brain, it seems, cares quite a lot about what we do for our blood sugar. Which drugs we choose to manage it might matter more than we realized.