• Type 2 diabetes is associated with an increased risk of Alzheimer’s and Parkinson’s.
• According to a new study, certain diabetes medications may significantly reduce this risk.
• These drugs, called gliflozins or SGLT2 inhibitors, stop the kidneys from reabsorbing too much blood glucose to improve blood sugar levels.
• Although the results of the study are encouraging, the authors call for more research to confirm their findings.

A team of scientists in Korea recently investigated a group of diabetes medications called gliflozins, or sodium-glucose cotransporter-2 (SGLT2) inhibitors.

They wanted to understand whether these drugs might reduce the risk of neurodegenerative conditions in people with type 2 diabetes (T2D).

Their analysis showed that compared to people taking other diabetes medications, those who took gliflozins were:

• 19% less likely to develop Alzheimer’s
• 20% less likely to develop Parkinson’s
• 31% less likely to develop vascular dementia

The study was published in the online issue of Neurology on September 18.

“The results are generally consistent even after adjusting for factors like blood pressure, glucose, cholesterol, and kidney function,” study author Minyoung Lee, MD, from Yonsei University College of Medicine in South Korea, said in a news release.

SGLT2 inhibitors lowered dementia, Parkinson’s risk by 22%

For this study, the researchers accessed data from 358,862 participants with type 2 diabetes and followed them for an average of 9.6 years.

By the study’s end, 6,837 participants had developed either dementia or Parkinson’s disease.

Overall, gliflozin use was associated with a 22% lower risk of developing either dementia or Parkinson’s.

When the researchers broke down the risk of specific neurodegenerative conditions, they found a 19% reduction in Alzheimer’s risk, a 20% reduction in Parkinson’s risk, and a 31% reduction in vascular dementia risk.

Daniel Truong, MD, a neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, shared his thoughts on the study findings with Healthline.

He said he was surprised “how consistent the benefits were across various subgroups of patients, including those with different comorbidities, such as cardiovascular disease or hypertension.” Truong was not involved in the study.

SGLT2 inhibitors help protect against neurodegenerative diseases

Gliflozins or SGLT2 inhibitors work by stopping the kidneys from reabsorbing as much glucose. This allows the body to remove the glucose in urine rather than re-entering the blood.

SGLT2 inhibitors are considered a second-line medication. In other words, doctors tend to prescribe them if a current diabetes medication is not working well enough.

Recently, there has been growing interest in this class of drugs and their protective effects against neurodegenerative conditions.

For instance, another Korean study published last month concluded that taking gliflozins was associated with a 35% lower risk of developing dementia compared with taking another common diabetes drug.

The latest study took a similar approach but also studied the impact of gliflozins on Parkinson’s disease.

In addition, the scientists compared gliflozins with a range of other diabetes medications, rather than the singular comparison drug in the previous study.

What’s the link between diabetes and neurodegenerative diseases?

Insulin primes the body’s cells to absorb blood sugar more efficiently, thereby lowering blood sugar levels.

In type 2 diabetes, however, individuals can become insulin resistant, which means that cells stop responding adequately to insulin and no longer take up glucose as efficiently.

Evidence is mounting that insulin resistance in the brain plays an important part in neurodegenerative conditions. As blood sugar levels rise, sensitive brain cells can become damaged.

A recent meta-analysis, for instance, found that diabetes is associated with a significantly higher risk of developing dementia.

Similarly, individuals with type 2 diabetes have a 21% increased risk of developing Parkinson’s disease. Evidence also suggests that the condition may progress more quickly in people with type 2 diabetes.

“An appropriate response to insulin is important not only for the pancreas and many organs in the body but also for the brain,” explained Alvaro Pascual-Leone, MD, professor of neurology at Harvard Medical School and chief medical officer and co-founder of Linus Health. Pascual-Leone was not involved in the study.

“Insulin resistance may play a key role in the link between type 2 diabetes and Alzheimer’s disease, but also other causes of dementia,” he told Healthline.

Combining metformin with gliflozins may further reduce risk

As diabetes prevalence increases, more people may face higher risks of developing neurodegenerative conditions as they grow older.

While the study authors suggest that gliflozins may just slow the progress of neurodegeneration, rather than stop it altogether, this would significantly benefit the aging population, nonetheless.

Still, the study does have some limitations. The researchers note because these neurodegenerative conditions take many years to develop, some people who did not develop dementia or Parkinson’s during the study might develop these conditions later.

“More research is needed to validate the long-term validity of these findings,” Lee said.

The study also leaves us with some unanswered questions.

For instance, the authors wonder whether starting treatment with gliflozins earlier might reduce the risk of neurodegeneration even further. This may be another reason why it’s best to start treatment as soon as possible.

Also, the researchers found that combining metformin with gliflozins reduced Parkinson’s and dementia risk to a greater extent than any other combination of drugs.

This raises the tantalizing possibility that drug combinations might be even more effective.

“To optimize antidiabetic drug use in clinical practice for neurodegenerative diseases, future research should evaluate the synergistic association of [gliflozins] with various combination therapies,” the authors wrote.

Could gliflozins reduce dementia risk in people without diabetes?

It’s currently unclear whether gliflozins could also reduce the risk of neurodegenerative conditions in people without type 2 diabetes.

“Further research needs to be done to determine if gliflozins can be neuroprotective and improve brain health and decrease dementia in people without diabetes,” explained Clifford Segil, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study.

“With their widespread use, it should be clear within a decade whether this is true. We may know the answer by 2035,” Segal added.

Truong noted these drugs do “have the potential to form the basis for future anti-dementia drugs, particularly for people at increased risk of developing dementia.”

“Their ability to improve brain metabolism, reduce inflammation, and protect cardiovascular health aligns with the primary risk factors and mechanisms driving dementia,” he continued.

“These significant effects on reducing the risk of dementia and neurodegenerative diseases represent an exciting development in diabetes care with broader implications for public health,” Truong concluded.

Takeaway

A recent study concludes that people with type 2 diabetes who take a class of drugs called gliflozins or SGLT2 inhibitors have a significantly reduced risk of developing dementia and Parkinson’s disease.

Although further research is needed, the results add to existing evidence showing the effects of gliflozins on slowing neurodegeneration.