A surprising ally: diabetes drugs fight dementia

Research from Korea suggests that SGLT-2 inhibitors not only treat type 2 diabetes, but can also reduce the risk of dementia by 35% compared to DPP-4 inhibitors.

Since the incidence of dementia is expected to increase rapidly, these findings underscore the need for further studies to investigate and confirm the potential neuroprotective effects of these drugs.

SGLT-2 inhibitors and dementia prevention

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors used to treat type 2 diabetes may prevent dementia and offer greater benefits with longer treatment, according to a large Korean study published today (28 August) by The BMJ.

Since this was an observational study, the researchers point out that the effect size may have been overestimated. Randomized controlled trials are now needed to confirm these results.

According to the World Health Organization, the number of people with dementia worldwide is expected to rise to 78 million by 2030. Type 2 diabetes is associated with a higher risk of developing dementia.

Study details and first results

A recent study of people over 65 with type 2 diabetes suggested a lower risk of dementia associated with SGLT-2 inhibitors compared with another diabetes drug, dipeptidyl peptidase-4 (DPP-4) inhibitors. The impact on younger people and certain types of dementia (e.g. Alzheimer disease, vascular dementia) remains unclear.

To investigate this issue, researchers used the Korean National Health Insurance Service database to identify 110,885 pairs of adults with type 2 diabetes aged 40 to 69 years who were free of dementia and had started taking an SGLT-2 inhibitor or a DPP-4 inhibitor between 2013 and 2021.

All participants (mean age 62 years, 56% men) were matched for age, sex, use of the diabetes drug metformin, and baseline cardiovascular risk and followed for an average of 670 days to determine who developed dementia.

Observational data and dementia risk reduction

In addition, possible influencing factors such as personal characteristics, income level, underlying risk factors for dementia, other diseases and associated medication use were taken into account.

During the follow-up period, a total of 1,172 participants with newly diagnosed dementia were identified.

The dementia rate per 100 person-years was 0.22 for those using SGLT-2 inhibitors and 0.35 for those using DPP-4 inhibitors, representing a 35% reduced risk of dementia with SGLT-2 inhibitor use compared with DPP-4 inhibitors.

The researchers also found that SGLT-2 inhibitors reduced the risk of Alzheimer's disease by 39 percent and the risk of vascular dementia by 52 percent compared to DPP-4 inhibitors.

In addition, the effect of SGLT-2 inhibitors appeared to be more pronounced with longer treatment duration. A 48% reduced risk of dementia was observed with treatment for more than two years, while it was reduced by 43% with treatment for two years or less.

Implications for clinical practice and future research

Because this is an observational study, no firm conclusions about cause and effect can be drawn. The authors point out that details about health behaviors (e.g. smoking and alcohol consumption) and duration of type 2 diabetes were not fully available.

However, they point out that this was a large-scale study based on nationally representative data, which also included relatively young people with type 2 diabetes, and that the results were extremely consistent across subgroups.

They believe that SGLT-2 inhibitors could prevent dementia and provide greater benefits with longer treatment and call for randomized controlled trials to confirm these findings.

This study reports promising results that have important implications for clinical practice as well as from a public health perspective, say researchers from Taiwan in a linked editorial.

They agree that further studies are needed to confirm these findings and suggest that studies are also needed “to explore the underlying mechanisms of any neuroprotective effects of SGLT-2 inhibitors.”

Because there is currently no cure for dementia and few effective treatment options are available, strategies that can potentially prevent the onset of the disease are critical, they write.

Given the significant socioeconomic and health burdens associated with both dementia and type 2 diabetes, they also recommend that clinical guidelines and health policies be regularly updated to reflect the latest and best evidence on the potential benefits of SGLT-2 inhibitors, including reduced risk of dementia.

Reference: “Risk of dementia after initiation of treatment with sodium-glucose cotransporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors in adults aged 40–69 years with type 2 diabetes: population-based cohort study” by Anna Shin, Bo Kyung Koo, Jun Young Lee and Eun Ha Kang, August 28, 2024, BMJ.
DOI: 10.1136/bmj-2024-079475