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SEONGNAM, South Korea — A popular class of drug used to manage Type 2 diabetes may also help reduce the risk of future dementia, researchers reveal. Their new study, published in The BMJ, reports on the benefits of using sodium-glucose cotransporter-2 (SGLT-2) inhibitors, as they were associated with fewer dementia cases than people taking dipeptidyl peptidase-4 (DPP-4) inhibitors.
An observational study tracked the health outcomes of adults living with Type 2 diabetes who were dementia-free at the time and taking either an SGLT-2 inhibitor or a DPP-4 inhibitor — two different types of diabetes medications.
In total, 1,172 people in the group developed some form of dementia during the study. However, people taking SGLT-2 inhibitors had fewer dementia cases than those taking DPP-4 inhibitors. For example, researchers calculated there was more than a 50% lower chance of developing vascular dementia when patients were taking SGLT-2 inhibitors. Another observation researchers noticed is that people were less likely to have dementia the longer they were on SGLT-2 inhibitor treatment.
In total, Korean researchers tracked the dementia outcomes of 110,885 adults with Type 2 diabetes who were dementia-free at the start of the study and between the ages of 40 and 69. Their data was taken from the Korea National Health Insurance Service Database. All adults had taken an SGLT-2 inhibitor or a DPP-3 inhibitor between 2013 and 2021. Each participant was followed up with after 670 days.
Researchers calculated there was more than a 50% lower chance of developing vascular dementia when patients were taking SGLT-2 inhibitors. (© Katsiaryna – stock.adobe.com)
What are SGLT-2 inhibitors?
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a type of medication used to treat Type 2 diabetes. They work by helping the kidneys remove excess glucose (sugar) from the body through urine. Normally, the kidneys filter out glucose, but some of it is reabsorbed back into the blood. SGLT-2 inhibitors block this reabsorption, so more glucose is excreted, which helps lower blood sugar levels.
In addition to controlling blood sugar, these medications may also offer other health benefits, such as protecting the heart and kidneys. Common SGLT-2 inhibitors include drugs like empagliflozin (Jardiance®), dapagliflozin (Farxiga®), and canagliflozin (Invokana®).
The World Health Organization reports global dementia cases are expected to rise to 78 million by 2030. As there is no cure for dementia and only limited treatment options, there is a greater demand for preventing the condition altogether.
However, it’s important to consider the study design for this research. The authors conducted an observational study, meaning other factors contributing to dementia could have been the reason behind differences in dementia rates. For example, no information was collected on how often people smoked, drank, or how long they had been diagnosed with Type 2 diabetes.
The findings also cannot prove cause and effect. There is no data to support that diabetes causes dementia. However, research has observed a strong link between Type 2 diabetes and a greater risk of developing dementia for some time now. Still, the findings give promising results for future strategies to reduce dementia risk, especially among younger adults, since the study collected a large amount of data that included younger people with Type 2 diabetes.
Paper Summary
Methodology
This study, led by Anna Shin, employed a population-based cohort design to evaluate the risk of dementia in adults aged 40-69 years with Type 2 diabetes, specifically comparing those who initiated sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors. The researchers utilized data from the Korean National Health Insurance Service, covering the period from 2013 to 2021. The study included 110,885 matched pairs of participants, all of whom had no prior diagnosis of dementia and had not used either of the study drugs in the year preceding their inclusion in the study.
Propensity score matching was used to balance covariates between the groups, ensuring comparability. The primary outcome was the onset of dementia, with secondary outcomes including dementia requiring drug treatment and specific types of dementia, such as Alzheimer’s disease and vascular dementia. The researchers applied Cox proportional hazard models to estimate hazard ratios, and follow-up was stratified by duration (greater than two years versus two years or less) to assess the impact of treatment duration.
Key Results
The study found that people who took SGLT-2 inhibitors had a lower chance of getting dementia compared to those who took DPP-4 inhibitors. For every 100 people who took SGLT-2 inhibitors, about 22 were diagnosed with dementia, while 35 out of every 100 people taking DPP-4 inhibitors were diagnosed. This means that the risk of getting dementia was about 35% lower for those on SGLT-2 inhibitors.
The study also looked at how long people were on the medication. It found that people who took SGLT-2 inhibitors for more than two years had an even lower risk of getting dementia than those who took it for two years or less. This reduced risk was seen in all types of dementia, including Alzheimer’s disease, and was true for different groups of people, no matter their age, gender, or other health conditions.
Study Limitations
As with any observational study, the potential for residual confounding cannot be entirely excluded, despite the robust methodology employed. The study relied on claims data, which may not capture all relevant clinical nuances or the onset of dementia symptoms prior to diagnosis.
Additionally, while propensity score matching helped balance many confounding variables, unmeasured factors could still influence the results. The relatively short follow-up period for some participants (mean follow-up of 670 days) may also limit the ability to fully assess the long-term effects of SGLT-2 inhibitors on dementia risk.
Discussion & Takeaways
This study adds to the growing body of evidence suggesting that SGLT-2 inhibitors may offer neuroprotective benefits, potentially reducing the risk of dementia in adults with Type 2 diabetes. The results were particularly compelling for those who remained on the treatment for more than two years.
The findings support the hypothesis that SGLT-2 inhibitors might influence dementia risk through mechanisms beyond glucose control, possibly involving direct neuroprotective effects or improved cardiovascular outcomes. However, due to the observational nature of the study, these findings should be interpreted with caution, and randomized controlled trials are necessary to confirm these results.
Funding & Disclosures
The study was conducted using data from the Korean National Health Insurance Service, and the authors disclosed no specific funding sources or conflicts of interest in the publication.
