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. 2021 Oct 21:8:747620.
doi: 10.3389/fcvm.2021.747620. eCollection 2021.

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors vs. Dipeptidyl Peptidase-4 (DPP4) Inhibitors for New-Onset Dementia: A Propensity Score-Matched Population-Based Study With Competing Risk Analysis

Jonathan V Mui  1 , Jiandong Zhou  2 , Sharen Lee  1 , Keith Sai Kit Leung  3 , Teddy Tai Loy Lee  3 , Oscar Hou In Chou  3 , Shek Long Tsang  1 , Abraham Ka Chung Wai  3 , Tong Liu  4 , Wing Tak Wong  5 , Carlin Chang  6 , Gary Tse  4   7 , Qingpeng Zhang  1
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Free PMC article

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors vs. Dipeptidyl Peptidase-4 (DPP4) Inhibitors for New-Onset Dementia: A Propensity Score-Matched Population-Based Study With Competing Risk Analysis

Jonathan V Mui et al. Front Cardiovasc Med. .
Free PMC article

Abstract

Introduction: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset cognitive dysfunction in type 2 diabetes mellitus remain unknown. This study aimed to evaluate the effects of the two novel antidiabetic agents on cognitive dysfunction by comparing the rates of dementia between SGLT2I and DPP4I users. Methods: This was a population-based cohort study of type 2 diabetes mellitus patients treated with SGLT2I and DPP4I between January 1, 2015 and December 31, 2019 in Hong Kong. Exclusion criteria were <1-month exposure or exposure to both medication classes, or prior diagnosis of dementia or major neurological/psychiatric diseases. Primary outcomes were new-onset dementia, Alzheimer's, and Parkinson's. Secondary outcomes were all-cause, cardiovascular, and cerebrovascular mortality. Results: A total of 13,276 SGLT2I and 36,544 DPP4I users (total n = 51,460; median age: 66.3 years old [interquartile range (IQR): 58-76], 55.65% men) were studied (follow-up: 472 [120-792] days). After 1:2 matching (SGLT2I: n = 13,283; DPP4I: n = 26,545), SGLT2I users had lower incidences of dementia (0.19 vs. 0.78%, p < 0.0001), Alzheimer's (0.01 vs. 0.1%, p = 0.0047), Parkinson's disease (0.02 vs. 0.14%, p = 0.0006), all-cause (5.48 vs. 12.69%, p < 0.0001), cerebrovascular (0.88 vs. 3.88%, p < 0.0001), and cardiovascular mortality (0.49 vs. 3.75%, p < 0.0001). Cox regression showed that SGLT2I use was associated with lower risks of dementia (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: [0.27-0.61], P < 0.0001), Parkinson's (HR:0.28, 95% CI: [0.09-0.91], P = 0.0349), all-cause (HR:0.84, 95% CI: [0.77-0.91], P < 0.0001), cardiovascular (HR:0.64, 95% CI: [0.49-0.85], P = 0.0017), and cerebrovascular (HR:0.36, 95% CI: [0.3-0.43], P < 0.0001) mortality. Conclusions: The use of SGLT2I is associated with lower risks of dementia, Parkinson's disease, and cerebrovascular mortality compared with DPP4I use after 1:2 ratio propensity score matching.

Keywords: Alzheimer's disease; DPP4; DPP4 inhibitor; Parkinson's disease; SGLT2; SGLT2 (sodium-glucose cotransporter 2) inhibitor; cognitive dysfunction; dementia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Procedures of data processing for the study cohort.
Figure 2
Figure 2
Cumulative incidence curves for new-onset cognitive dysfunctions stratified by the drug use of SGLT2I and DPP4I after propensity score matching (1:2).
Figure 3
Figure 3
Cumulative incidence curves for mortality outcomes stratified by the drug use of SGLT2I and DPP4I after propensity score matching (1:2).
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References

    1. Fung ACH, Tse G, Cheng HL, Lau ESH, Luk A, Ozaki R, et al. . Depressive symptoms, co-morbidities, and glycemic control in Hong Kong Chinese elderly patients with Type 2 diabetes mellitus. Front Endocrinol. (2018) 9:261. 10.3389/fendo.2018.00261 - DOI - PMC - PubMed
    1. Lee S, Zhou J, Wong WT, Liu T, Wu WKK, Wong ICK, et al. . Glycemic and lipid variability for predicting complications and mortality in diabetes mellitus using machine learning. BMC Endocr Disord. (2021) 21:94. 10.1186/s12902-021-00751-4 - DOI - PMC - PubMed
    1. Kovesdy CP, Isaman D, Petruski-Ivleva N, Fried L, Blankenburg M, Gay A, et al. . Chronic kidney disease progression among patients with type 2 diabetes identified in US administrative claims: a population cohort study. Clin Kidney J. (2021) 14:1657–64. 10.1093/ckj/sfaa200 - DOI - PMC - PubMed
    1. Folkerts K, Kelly AMB, Petruski-Ivleva N, Fried L, Blankenburg M, Gay A, et al. . Cardiovascular and renal outcomes in patients with type-2 diabetes and chronic kidney disease identified in a United States administrative claims database: a population cohort study. Nephron. (2021) 145:342–52. 10.1159/000513782 - DOI - PubMed
    1. Shin JY, Roh SG, Lee NH, Yang KM. Influence of epidemiologic and patient behavior-related predictors on amputation rates in diabetic patients: systematic review and meta-analysis. Int J Low Extrem Wounds. (2017) 16:14–22. 10.1177/1534734617699318 - DOI - PubMed