Some diabetes drugs may help lower risk

• The rate of neurodegenerative conditions is growing globally, meaning that a lot of research is into prevention of these problems.
• There has been some research suggesting that a type of type 2 diabetes drugs called SGLT2 inhibitors could reduce the incidence of some neurodegenerative conditions including Parkinson’s disease and Alzheimer’s disease.
• Now, a large cohort study has shown use of these drugs is associated with a lower risk of developing these neurodegenerative conditions.

Parkinson’s disease and Alzheimer’s disease risk are lowered in people who take a type of type 2 diabetes drug, a study from South Korea has shown.

Minyoung Lee, MD, PhD, of Yonsei University College of Medicine in Seoul, South Korea, and co-author of the paper explained to Medical News Today the premise of her and her colleagues’ study.

“Common pathophysiological links between type 2 diabetes and neurodegenerative diseases have been proposed, and individuals with type 2 diabetes are considered at high risk for neurodegenerative conditions,“ she told us. “Consequently, there has been research into whether diabetes medications might offer benefits for neurodegenerative diseases, but no drug has yet shown definitive evidence.“

“When I began my research, SGLT2 inhibitors had been introduced as a new treatment for diabetes. These drugs not only lower blood sugar but also increase urinary glucose excretion, which leads to reduced insulin levels and elevated ketone bodies in the body. Since ketones are known to be beneficial metabolites for the nervous system, I hypothesized that the unique pharmacological action of SGLT2 inhibitors might make them particularly beneficial in reducing the risk of neurodegenerative diseases,” explained Lee.

Steve Allder, MD, who is a consultant neurologist at Re:Cognition Health, and was not involved in this research, suggested to MNT that “The mechanism behind the neuroprotective effects of SGLT2 inhibitors is likely multifaceted, involving cardiovascular, metabolic and cellular effects.“

“SGLT2 inhibitors reduce common risk factors associated with dementia and Parkinson’s disease, such as hyperglycemia, insulin resistance, obesity, hypertension, and heart failure. These factors contribute to both vascular dementia and Alzheimer’s disease. By improving cardiovascular health, SGLT2 inhibitors are likely to help prevent cerebrovascular damage and neurodegeneration.”

To investigate whether or not use of SGLT2 inhibitors impacted risk of neurodegenerative conditions, researchers analyzed data on a cohort of 358,862 participants with type 2 diabetes.

Participants who had started taking SGLT2 inhibitors between 2014–2019 were matched with participants who were on other oral antidiabetes medications. All participants were over 40 years old.

The analysis showed that over a follow-up period of an average of 2.06 years for people on SGLT2 inhibitors, and 3.70 years for people on different antidiabetes drugs, there was a reduction in the risk of developing all-cause dementia in the group who took SGLT2 inhibitors of 21%.

In addition to this, a decrease of 20% incidence of Parkinson’s disease, as well as a 19% decrease in incidence of Alzheimer’s disease was observed in the group. Risk of vascular dementia was 31% lower.

Daniel Truong, MD, a neurologist, 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, who was not involved in the research, told MNT that:

“Another surprising finding is the larger benefit seen in younger populations (<65 or <70 years old) compared to older participants. This age-specific impact highlights the importance of early intervention in high-risk individuals with type 2 diabetes.”

The study authors say that the results show there are potential benefits for patients with type 2 diabetes taking SGLT2 inhibitors, which is important as they are at increased risk of neurological disease. However, they point out the study is observational and requires further study to determine how long-term this reduced risk is.

Lee told us: “I consider that the effect of SGLT2 inhibitors on neurodegenerative disease could be closer to the concept of attenuating the degenerative process and delaying the onset of dementia, rather than the concept of preventing dementia so that it never occurs.“

“At the population level, reducing the population at risk of dementia and changing social condition could be translated into ‘prevention.’ However, the meaning of prevention from the perspective of a single individual may differ from the population view, as it may imply an expectation of no incidence in their lifetime,” she cautioned.

Further work was needed to elucidate the mechanism behind the observed reduction in risk, said Lee. “I am engaged in research using a mouse model of dementia associated with metabolic disorders to explore how SGLT2 inhibitors positively affect neurodegenerative diseases,“ she noted.

“Previous studies have assessed the drug’s potential using a nationwide database from a broader perspective; however, my current work is dedicated to mechanistic studies that aim to elucidate these effects,” Lee told MNT.