Diabetes drug linked to reduced risk for several types of dementia

Key takeaways:

• SGLT2 inhibitor use reduced the risk for dementia by 35% vs. DDP-4 inhibitor use.
• Longer use of SGLT2 inhibitors linked to increased reductions of dementia risk.

Type 2 diabetes has emerged as a possible risk factor contributing to the development of dementia, but one class of agents used to treat the disease may provide greater protective effects, study results published in BMJ showed.

Findings from the population-based cohort study suggest that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduced the risk for dementia compared with the use of dipeptidyl peptidase-4 (DDP-4) inhibitors.

According to Anna Shin, a senior researcher from the Seoul National University Bundang Hospital in Korea, and colleagues, a recent study found an association between new users of SGLT2 inhibitors and a 20% to 34% reduced risk of dementia among people aged older than 66 years compared with new users of DDP-4 inhibitors.

“The effects on younger populations and specific types of dementia (eg, Alzheimer’s disease, vascular dementia) were not, however, examined,” they wrote. “Moreover, it is unclear whether different patient characteristics such as concomitant treatment or comorbidity status would modify such drug effects.”

Shin and colleagues aimed to fill in this knowledge gap by using the Korea National Health Insurance Service database to identify 110,885 pairs of adults aged 40 to 69 years with type 2 diabetes who started using either DDP-4 inhibitors or SGLT2 inhibitors between 2013 to 2021.

New-onset dementia served as the study’s primary outcome measurement, with secondary outcomes that evaluated each drug class’s effect on different types of dementia and dementia that required drugs.

At a mean follow-up of 670 ± 650 days, researchers reported 1,172 people diagnosed with dementia. They calculated dementia rates per 100 person-years of 0.22 among those using SGLT2 inhibitors and 0.35 among those using DPP-4 inhibitors.

The researchers found that vs. DPP-4 inhibitor use, SGLT2 inhibitor use was associated with a:

• 35% reduced risk for dementia (HR = 0.65; 95% CI 0.58-0.73);
• 39% reduced risk for Alzheimer’s disease (HR = 0.61; 0.53-0.69); and
• 52% reduced risk for vascular dementia (HR = 0.48; 0.33-0.7).

SGLT2 inhibitor use additionally reduced the risk for dementia requiring drugs (HR = 0.54; 0.46-0.63).

Study investigators also noted that the length of treatment influenced the protective effects of SGLT2 inhibitors also influenced by the length of treatment time. For example, they reported 48% reduced risk for dementia associated with more than 2 years of treatment (HR = 0.57, 95% CI, 0.46-0.7) compared with a 43% reduced risk tied to treatment of 2 years or less (HR = 0.52; 95% CI, 0.41-0.66).

The study could not prove causality because of its observational nature, Shin and colleagues noted. Additionally, overestimation may have been possible due to dementia diagnoses being commonly delayed.

“These findings underscore the need for future randomized controlled trials,” the researchers wrote.

In an accompanying editorial, Sung-Yun Tu, an attending physician at Dalin Tzu Chi Hospital in Tawain, and colleagues explained that “strategies that can potentially prevent onset [dementia] are critically important” because no cures currently exist and effective treatment options are limited.

Clinical guidelines and health care policies should be regularly updated to reflect the latest evidence on SGLT2 inhibitors and dementia risk, “given the substantial socioeconomic and public health burdens associated with both dementia and type 2 diabetes,” they wrote.

References:

• Certain diabetes drugs might prevent dementia. https://bmjgroup.com/certain-diabetes-drugs-might-prevent-dementia/#. Published Aug. 28, 2024. Accessed Sept. 10, 2024.
• Shin A, et al. BMJ. 2024;doi:10.1136/bmj-2024-079475.
• Tu S, et al. BMJ. 2024;doi:10.1136/bmj.q1841.