hands holding pen writing in notebookShare on Pinterest
SGLT-2 inhibitors have been linked with a 35% lower dementia risk in a recent study. Image credit: Tanya Yatsenko/Stocksy.
  • People who have type 2 diabetes are at an increased risk of developing dementia.
  • A recent study investigates how a diabetes medication may affect this risk.
  • The scientists behind the study focused on sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which they found significantly reduced dementia risk compared with another diabetes drug.
  • The longer an individual had been taking the drug, the greater the protective effect was.

The results of a new large-scale study published in The BMJ suggest that a relatively new diabetes drug might reduce the risk of developing dementia in people with type 2 diabetes.

Taking SGLT-2 inhibitors was associated with a 35% lower risk of developing dementia compared with taking another common diabetes drug with a different mechanism.

Although the authors call for more research, as dementia prevalence is on the rise, the results of the current study are encouraging.

Currently, the world is experiencing what some researchers have termed a “dementia epidemic.” The primary risk factor for dementia is aging. So, as the average age of the population increases, so does the number of dementia cases.

Aging is not the only risk factor, however. According to recent research, developing type 2 diabetes is linked to an increase in the risk of developing dementia of 50%.

Because type 2 diabetes is on the rise in the United States and elsewhere, this may also help fuel the epidemic.

Speaking to Medical News Today asked Raj Dasgupta, MD, chief medical advisor for Fortune Recommends Health, who was not involved in the current study, explained why the two conditions are linked. He said that:

“People with type 2 diabetes have a higher risk of dementia because the same cardiovascular problems that increase the risk of type 2 diabetes also increase the risk of dementia. The main problem is that high blood sugar levels over time can damage blood vessels in the brain, leading to less blood and oxygen reaching brain cells.”

According to Dasgupta, the resulting brain cell damage can cause cognitive decline and increase the risk of vascular dementia — a form of dementia characterized by disruption to the brain’s blood supply.

He also explained that insulin resistance, which is a hallmark of type 2 diabetes, “affects brain cells and is linked to a higher chance of Alzheimer’s disease.”

Dasgupta further told MNT that other factors associated with type 2 diabetes can increase dementia risk, including:

SGLT-2 inhibitors are relatively new drugs that treat type 2 diabetes. The first SGLT-2 inhibitor approved for use in the United States was dapagliflozin (Farxiga), in 2014.

These drugs stop the kidneys from reabsorbing as much glucose, allowing the body to remove the glucose in urine rather than it re-entering the blood.

Doctors now regularly prescribe SGLT-2 inhibitors to treat diabetes if their current medication is not controlling their condition adequately. Currently, around 1 in 10 people in the U.S. with type 2 diabetes take these medications.

A range of FDA-approved SGLT-2 inhibitors are now available, including canagliflozin (Invokana), empagliflozin (Jardiance), and ertugliflozin (Steglatro).

Beyond their benefits for people with type 2 diabetes, some studies suggest these drugs might also reduce the risk of dementia.

However, according to the authors of the latest study, this previous research has significant gaps. To build a clearer picture, they conducted a large-scale observational study.

To investigate the drug’s links to dementia risk, the researchers compared people with type 2 diabetes taking SGLT-2 inhibitors with those taking dipeptidyl peptidase-4 (DPP-4) inhibitors.

DPP-4 inhibitors are another class of anti-diabetes drugs with a different mechanism. These oral medications work by increasing levels of glucagon-like peptide-1 (GLP-1), which increases insulin production, thereby reducing blood sugar levels.

The scientists used Korean National Health Insurance Service data from 2013–2021. This included 110,885 people with type 2 diabetes ages 40–69, all of whom were taking either SGLT-2 or DPP-4 inhibitors.

They matched participants for age and sex, and controlled for a wide range of variables, including income, ongoing medical conditions, and other dementia risk factors, like smoking.

During follow-up, which was an average of 670 days, there were 1,172 new diagnoses of dementia within the participants.

Compared with those taking DPP-4 inhibitors, participants on SGLT-2 inhibitors had a 35% reduced risk of developing dementia.

When the scientists looked at dementia subtypes, they found that SGLT-2 inhibitors were linked to 52% lower risk of vascular dementia, and 39% lower risk of Alzheimer’s disease.

Importantly, the risk reduction was most pronounced in those who had been taking SGLT-2 inhibitors for longer — more than 2 years compared with less than 2 years.

Overall, the authors conclude that “SGLT-2 inhibitors might prevent dementia, providing greater benefits with longer treatment.”

However, because the study was observational, they explain that the effect size might be “overestimated.” Nevertheless, because the study was large, and the effect was clear in all the subgroups, the results are relatively robust.

Even so, the scientists call for randomized controlled trials to confirm their findings.

Akhil Shenoy, MD, an endocrinologist and medical advisor at Aeroflow Diabetes, explained to MNT how people with type 2 diabetes can reduce their dementia risk.

He suggested “maintaining normal blood pressure and blood sugar levels, a healthy body weight, and at least low to moderate levels of physical activity.”

Shenoy, who was not involved in the study, also advised people to avoid tobacco.

MNT also spoke to Angel Luk, RD, a registered dietitian and nutritionist who was not involved in the study, asking about dietary interventions that might reduce risk.

“Reducing alcohol intake, eating more fiber-rich foods such as whole grains, vegetables, and fruit, and finding practical ways to manage stress” are important, she said.

Finally, MNT spoke with Clifford Segil, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study.

“People with diabetes who monitor their glucose levels and use medications are more likely to avoid organ damage, including kidney damage, nerve damage, and vascular dementia,” he said.

If future research confirms the results of the latest study, SGLT-2 inhibitors may also be a useful tool to help stem the dementia epidemic. However, while dementia risk is higher in people with type 2 diabetes, it is not inevitable.

Managing diabetes with medication, and making healthy lifestyle changes could significantly reduce a person’s dementia risk.