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• Posted August 12, 2021

Some Diabetes Meds Might Also Lower Alzheimer's Risk

Older adults who take certain diabetes drugs may see a slower decline in their memory and thinking skills, a new study suggests.

Researchers in South Korea found that among older people who'd been having memory issues, those using diabetes drugs called DDP-4 inhibitors typically showed a slower progression in those symptoms over the next few years. That was compared with both diabetes-free older adults and those taking other diabetes medications.

People on DDP-4 inhibitors also showed smaller amounts of the "plaques" that build up in the brains of people with Alzheimer's disease.

Experts cautioned that the findings do not prove the drugs can prevent or delay dementia.

To do that, researchers would need to conduct clinical trials that directly test the medications, said Dr. Howard Fillit, chief science officer for the nonprofit Alzheimer's Drug Discovery Foundation in New York City.

But, he said, the study adds to evidence that certain existing medications -- including some for diabetes or high blood pressure -- could be "repurposed" for protecting the aging brain.

In fact, other diabetes medications, such as metformin and GLP-1 agonists, are already being studied for slowing down declines in memory and thinking skills.

There has been less research, Fillit said, into DDP-4 inhibitors -- which include oral medications like sitagliptin (Januvia), linagliptin (Tradjenta), saxagliptin (Onglyza) and alogliptin (Nesina). They share a similarity with GLP-1 agonists, in that they act on the same "pathway" in the body.

Fillit explained that DDP-4 inhibitors work by boosting blood levels of GLP-1, a gut hormone that stimulates insulin release. Insulin is a hormone that regulates blood sugar.

People with diabetes are resistant to insulin, which results in chronically high blood sugar levels. Some studies have found that people with Alzheimer's also have problems with insulin resistance -- and researchers have speculated that may contribute to the brain degeneration seen in the disease.

But Fillit said that diabetes medications might have effects beyond improving insulin resistance.

Animal research has suggested DDP-4 inhibitors can reduce brain inflammation and protect brain cells from Alzheimer's-like injury.

For the current study, researchers led by Dr. Phil Hyu Lee of Yonsei University College of Medicine in Seoul reviewed the cases of 282 patients who had come to their clinic with complaints about their memory and thinking abilities. Brain scans had shown all had evidence of amyloid -- the protein that makes up Alzheimer's-related plaques.

Of those patients, half had diabetes: 70 were taking a DDP-4 inhibitor, and 71 were using other diabetes drugs, most often metformin and sulfonylureas.

On average, the researchers found, patients on DDP-4 inhibitors had less amyloid buildup than either the diabetes-free patients or those on other diabetes medications. And over the next few years, they also showed a slower decline on tests of memory and thinking.

The findings were published online Aug. 11 in the journal Neurology.

Maria Carrillo, chief science officer for the Alzheimer's Association, stressed that the study cannot prove DDP-4 inhibitors slow down the dementia process.

One of the study's limitations, she noted, is that patients' amyloid levels were only measured at the start. So it's not clear whether those on DDP-4 inhibitors had a slower accumulation of brain plaques over time.

It's well known, Carrillo said, that people with diabetes have a higher risk of developing Alzheimer's than those without diabetes -- though the reasons are not fully clear, she added.

Insulin resistance, as well as high blood sugar, may partly explain it, according to the Alzheimer's Association. Carrillo noted that this study did not look at patients' long-term blood sugar control -- and whether that had any role in their rates of decline over time.

"There is some rationale for looking at these diabetes drugs in people with Alzheimer's," Carrillo said.

But like Fillit, she said only randomized clinical trials -- where patients are randomly assigned to take a DDP-4 inhibitor or not -- can prove whether there are benefits.

One question for future studies, Fillit said, is whether DDP-4 inhibitors can slow mental decline in people without diabetes, or only those with the disease.

Because Alzheimer's is so complex, Fillit said it is likely that medication combinations -- aimed at different mechanisms behind the disease -- will prove most effective at treating or preventing the disease.

Both of the nonprofits encourage people to eat a healthy diet, exercise, avoid smoking and engage in mentally stimulating activities to help keep their bodies and minds in good shape as they age.

More information

The Alzheimer's Drug Discovery Foundation has more on protecting brain health.

SOURCES: Maria Carrillo, PhD, chief science officer, Alzheimer's Association, Chicago; Howard Fillit, MD, chief science officer, Alzheimer's Drug Discovery Foundation, New York City; Neurology, online, Aug. 11, 2021