Abstract
Study Objectives: Diabetes mellitus per se and its related therapy have been frequently associated with an increased risk of developing dementia. However, studies that explored the risk of dementia from the use of the novel oral antidiabetic medication dipeptidyl peptidase 4 inhibitor (DPP-4i) have been limited, especially in Asian populations. The present study aimed to determine the effect of DPP-4i on the subsequent risk of dementia among patients with type 2 diabetes (T2D) in Taiwan. Methods: This study utilized data from the Longitudinal Health Insurance Database between 2008 and 2015. We enrolled 2903 patients aged ≥50 years, who were on DPP-4i for a diagnosis of T2D and had no dementia. A total of 11,612 subjects were included and compared with a propensity score-matched control group who did not use DPP-4i (non-DPP-4i group). Survival analysis was performed to estimate and compare the risk of dementia—including Alzheimer’s disease, vascular dementia, and other dementia types—between the two groups. Results: Both groups had a mean age of 68 years, had a preponderance of women (61.8%), and were followed up for a mean duration of 7 years. The risk of all-cause dementia was significantly lower in the DPP-4i group than in the non-DPP-4i group (hazard ratio (HR) 0.798; 95% confidence interval (CI) 0.681–0.883; p < 0.001), with a class effect. This trend was particularly observed for vascular dementia (HR 0.575; 95% CI 0.404–0.681; p < 0.001), but not in Alzheimer’s disease (HR 0.891; 95% CI 0.712–1.265; p = 0.297). The Kaplan–Meier analysis showed that the preventive effect on dementia was positively correlated with the cumulative dose of DPP-4i. Conclusions: DPP-4i decreased the risk of dementia with a class effect, especially vascular dementia, but not in Alzheimer’s disease. Our results provide important information on the drug choice when managing patients with T2D in clinical practice.
Highlights
Diabetes mellitus is one of the major global health problems in an aging society
Our study demonstrated that compared with non-dipeptidyl peptidase 4 inhibitor (DPP-4i) use, DPP-4i use was associated with a 21% lower risk of developing all types of dementia in older patients with type 2 diabetes (T2D)
DPP-4 inhibitor, which is one of the incretin-based therapies that increase the concentration of circulating GLP-1, has been frequently used for the treatment of T2D because of its relatively low risk of inducing hypoglycemia [25]
Summary
Driven by aging and aging-related comorbidities, diabetes mellitus continues to increase in prevalence, in Taiwan, and around the world. In Taiwan, the prevalence of type 2 diabetes (T2D) was reported by community studies to be up to 26.9% among those aged over 65 years [1]. The prevalence of dementia accounted for 2% to 5% of the population aged over 65 years [2], and this has placed a heavy burden on dementia patients, their caregivers and the community [3,4,5]. A previous study disclosed that diabetes mellitus was associated with a 1.7-fold greater risk of dementia among elderly people [10]. T2D was a significant risk factor for AD, and for vascular dementia [11]
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