Sodium glucose cotransporter-2 (SGLT-2) inhibitors used to treat type 2 diabetes may prevent dementia, providing greater benefits with longer treatment, suggests a large study from Korea published by The BMJ Today.
Because this study was observational, the researchers note that the effect size could have been overestimated and say that randomized controlled trials are now needed to confirm these findings.
According to the World Health Organization, the number of people living with dementia is expected to reach 78 million worldwide by 2030 and type 2 diabetes is associated with a greater risk of developing dementia.
A recent study of people over 65 with type 2 diabetes suggested a reduced risk of dementia associated with SGLT-2 inhibitors compared with another type of diabetes drug, dipeptidyl peptidase-4 (DPP-4) inhibitors. But the effects on younger people and specific forms of dementia (e.g. Alzheimer’s disease, vascular dementia) remain unclear.
To address this, researchers used the Korea National Health Insurance Service database to identify 110,885 pairs of adults with type 2 diabetes aged 40-69 who were free of dementia and had taken an SGLT-2 inhibitor or started taking a DPP-4 inhibitor. and 2021.
All participants (mean age 62; 56% men) were matched for age, gender, use of the diabetes drug metformin and baseline cardiovascular risk and were followed for an average of 670 days to see who developed dementia.
Potentially influential factors were also taken into account, including personal characteristics, income level, underlying risk factors for dementia, other conditions and related medication use.
A total of 1,172 participants with newly diagnosed dementia were identified during the follow-up period.
Dementia rates per 100 person-years were 0.22 for those taking SGLT-2 inhibitors and 0.35 for those taking DPP-4 inhibitors, corresponding to a 35% lower risk of dementia associated with SGLT-2 use inhibitors compared with DPP-4 inhibitors.
The researchers also found a 39% lower risk of Alzheimer’s disease and a 52% lower risk of vascular dementia associated with SGLT-2 inhibitors compared to DPP-4 inhibitors.
Furthermore, the effect of SGLT-2 inhibitors seemed more pronounced with longer treatment duration. A 48% lower risk of dementia was observed for more than two years of treatment, versus a 43% reduced risk for two years or less.
This is an observational study, so no firm conclusions can be drawn about cause and effect, and the authors note that details about health behaviors (for example, smoking and alcohol consumption) and duration of type 2 diabetes were not fully available.
However, they point out that this was a large study based on nationally representative data involving relatively younger people with type 2 diabetes, and that the results were very consistent across all subgroups.
As such, they say that SGLT-2 inhibitors may prevent dementia, providing greater benefits with longer treatment, and they call for randomized controlled trials to confirm these findings.
This study reports promising results that have important implications for clinical practice and 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 investigate 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 its onset are critical, they write.
Given the significant socio-economic and public health burdens associated with both dementia and type 2 diabetes, they also recommend that clinical guidelines and healthcare policies be regularly updated to reflect the latest best evidence on the potential benefits of SGLT-2 inhibitors, including reduced risk of dementia.
Source:
Magazine reference:
Shin, A., et al. (2024). Risk of dementia after initiating sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population-based cohort study. BMJ. doi.org/10.1136/bmj-2024-079475.