Diabetes Drugs May Lower Risk for Types of Dementia Among Older Adults

Compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium glucose cotransporter 2 (SGLT-2) inhibitors may result in a lower risk of developing different types of dementia in patients with type 2 diabetes (T2D), according to study results published in the British Medical Journal (BMJ).

Although researchers have previously compared the risk of developing dementia with the use of SGLT-2 and DPP-4 inhibitors, limitations in the design of these studies have led to unclear conclusions.

In a recent cohort study, researchers assessed dementia risk in adults with T2D who received treatment with an SGLT-2 or an DPP-4 inhibitor.

Eligible participants were aged between 40 and 69 years with T2D, initiated treatment with an SGLT-2 or DPP-4 inhibitor, and did not have dementia before the index date (first dispensing date of an SGLT-2 or DPP-4 inhibitor).

Primary study outcome was incident dementia, based on the International Classification of Diseases, Tenth Revision (ICD-10) codes. Secondary outcomes were dementia that required medications and other types of dementia, including Alzheimer disease (AD) and vascular dementia. Risk for positive and negative control outcomes, such as genital infections and osteoarthritis-related clinical encounters and cataract surgery, respectively, was also compared between the 2 treatment groups.

A total of 112,663 and 847,999 participants who initiated treatment with SGLT-2 and DPP-4 inhibitors, respectively, were eligible for the study. After propensity-score matching for covariates, 110,885 (mean age, 61.9; men, 55.7%) were included in each group.

Cardiometabolic comorbidities were common among participants, with approximately 66.5% having hypertension and approximately 78.6% having hyperlipidemia. The most common SGLT-2 and DPP-4 inhibitor prescribed was dapagliflozin (58.6%) and gemigliptin (22.7%), respectively.

During a mean follow-up of 670 days, 1176 participants received a dementia diagnosis. Incidence rate of developing dementia was 0.22 and 0.35 per 100 person-years with SGLT-2 and DPP-4 inhibitors, respectively (hazard ratio [HR], 0.65; 95% CI, 0.58-0.73).

For secondary outcomes, as well, dementia risk was reduced with the use of SGLT-2 vs DPP-4 inhibitors (dementia-requiring medications: HR, 0.54 [95% CI, 0.46-0.63]; AD: HR, 0.61 [95% CI, 0.53-0.69); and vascular dementia: HR, 0.48 [95% CI, 0.33-0.70]).

With regard to control outcomes, genital infections were approximately 3-fold risk with SGLT-2 vs DPP-4 inhibitors (HR, 2.67; 95% CI, 2.57-2.77), and approximately 1-fold risk with treatment for osteoarthritis-related encounters (HR, 0.97; 95% CI, 0.95-0.98) and cataract surgery (HR, 0.92; 0.89-0.96).

Results of the intention-to-treat and sensitivity analyses were consistent with results of the primary analysis. Findings from the subgroup analysis also showed lower risk with SGLT-2 vs DPP-4 inhibitors that was consistent across subgroups, stratified by age, sex, metformin use, and cardiovascular risk.

Limitations of the analysis were the observational nature of the study; delayed diagnoses of dementia that could have resulted in misclassification; and the lack of information on neuroprotection.

Overall, the researchers, concluded, “SGLT-2 inhibitors might prevent dementia, providing greater benefits with longer treatment.” They added, “[Randomized] controlled trials are needed to confirm these findings.”