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Some diabetes medications may also lower Alzheimer’s risk

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By Amy Norton
HealthDay Reporter

THURSDAY, Aug. 12, 2021 (HealthDay News) – Older adults who take certain diabetes medications may experience slower decline in their memory and thinking skills, a new study suggests.

Researchers in South Korea found that among older people who had memory problems, those using diabetes medications called DDP-4 inhibitors generally showed a slower progression in those symptoms over the next several years. That was compared to both older adults without diabetes and those taking other diabetes medications.

People taking 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 that the drugs can prevent or delay dementia.

To do that, researchers would have to conduct clinical trials that directly test the drugs, said Dr. Howard Fillit, scientific director of the nonprofit Alzheimer’s Drug Discovery Foundation in New York City.

But, he said, the study adds to the evidence that certain existing drugs, including some for diabetes or high blood pressure, could be “reused” to protect the aging brain.

In fact, other diabetes medications, such as metformin and GLP-1 agonists, are already being studied to slow the decline in memory and thinking skills.

There has been less research, Fillit said, on DDP-4 inhibitors, which include oral medications such as sitagliptin (Januvia), linagliptin (Tradjenta), saxagliptin (Onglyza) and alogliptin (Nesin). 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 increasing blood levels of GLP-1, an intestinal hormone that stimulates the release of insulin. Insulin is a hormone that regulates blood sugar.

People with diabetes are insulin resistant, 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 it may contribute to the brain degeneration seen in the disease.

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

Research in animals has suggested that DDP-4 inhibitors may reduce brain inflammation and protect brain cells from injury similar to Alzheimer’s disease.

For the current study, researchers led by Dr. Phil Hyu Lee of the Yonsei University School of Medicine in Seoul reviewed the cases of 282 patients who had come to their clinic with complaints about their memory and thinking ability. Brain scans had shown they 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 medications, most often metformin and sulfonylureas.

On average, the researchers found, patients taking DDP-4 inhibitors had less amyloid buildup than patients without diabetes or those taking other diabetes medications. And over the next several years, they also showed a slower decline on memory and thinking tests.

The findings appear in the Aug. 11 online issue of the journal. Neurology.

María Carrillo, scientific director of the Alzheimer’s Association, emphasized that the study cannot prove that DDP-4 inhibitors delay the dementia process.

One of the study’s limitations, he noted, is that the patients’ amyloid levels were only measured at the beginning. Therefore, it is not clear whether those who took DDP-4 inhibitors had a slower accumulation of brain plaques over time.

It is well known, Carrillo said, that people with diabetes have a higher risk of developing Alzheimer’s than those without diabetes, although the reasons are not entirely clear, he added.

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

“There are a few reasons to consider these diabetes medications in people with Alzheimer’s,” Carrillo said.

But like Fillit, he said that only randomized clinical trials, where patients are randomly assigned to take a DDP-4 inhibitor or not, can prove if 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 in those with the disease.

Because Alzheimer’s is so complex, Fillit said combinations of drugs, targeting different mechanisms behind the disease, are likely to be more effective in treating or preventing the disease.

Both 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 about protecting brain health.

SOURCES: Maria Carrillo, PhD, Scientific Director, Alzheimer’s Association, Chicago; Howard Fillit, MD, Chief Scientific Officer, Alzheimer’s Drug Discovery Foundation, New York; Neurology, online, August 11, 2021

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