The association between sodium-glucose cotransporter 2 inhibitors and incident dementia: A nationwide population-based longitudinal cohort study

Abstract

Background The association of the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor and incident dementia remains unclear. This study aimed to evaluate the risk of incident dementia with the use of SGLT2 inhibitor. Methods This is a population-based cohort study utilizing Taiwan’s National Health Insurance Research Database. Each patient who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas 1:1 propensity score-matched randomly selected patients who were nonusers of SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was incident dementia. Results A total of 976,972 patients newly diagnosed with type 2 diabetes mellitus (DM) between 2011 and 2018 were included in this study. After the patients’ propensity score matching by age, sex, duration of DM, comorbidities and drug index date of the patients, a total of 103,247 patients in the SGLT2 inhibitor group and 103,247 in the non-SGLT2 inhibitor group were enrolled for analysis. The SGLT2 inhibitor group was associated with a lower risk of incident dementia (adjusted hazard ratio: 0.89, 95% confidence interval: 0.82–0.96; p = .0021). Diabetic complications were significantly lower in the SGLT2 inhibitor group compared with the non-SGLT2 group. Sensitivity analysis was also consistent with the main analysis. Conclusions Patients with type 2 DM who were prescribed SGLT2 inhibitors were associated with a lower risk of incident dementia compared with those not prescribed SGLT2 inhibitors in real-world practice.

The impact of sodium‐glucose co‐transporter‐2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation

“…7,8 The superiority of SGLT2i over other antidiabetic agents in reducing incident dementia indicated that the protective effects of SGLT2i could be beyond glycaemic control. 8,9,33,35 The insignificant interaction between SGLT2i and DPP4i shown in our study exhibited the consistent benefits of SGLT2i irrespective of the use of DPP4i or not. Pleomorphic effects of SGLT2i have been proposed in the preclinical studies that can be the plausible mechanisms for mitigating the risks of cognitive decline, including reducing oxidative stress, neuroinflammation, and improving brain mitochondrial function.…”

“…31 Other antidiabetic medications such as metformin, DPP4i, and SGLT2i have been associated with a lower risk of dementia in patients with diabetes. [32][33][34] Previous literature mainly compared the efficacy between SGLT2i and DPP4i in reducing the risk of incident dementia. 7,8 The superiority of SGLT2i over other antidiabetic agents in reducing incident dementia indicated that the protective effects of SGLT2i could be beyond glycaemic control.…”

Comparison on cognitive outcomes of antidiabetic agents for type 2 diabetes: A systematic review and network meta‐analysis

“…As shown in Figure 1, we identified 15,995 abstracts and performed full‐text assessments of 39 articles. Twenty‐seven unique studies 13–39 (1,590,757 patients) met the inclusion criteria, including 3 RCTs, 19 cohort studies, and 5 case‐control studies. Thirty‐one articles were excluded due to the lack of high‐quality data.…”

“…Supplement Table and Supplement Table summarised the baseline metabolic index between antidiabetic medication users and non‐users. A total of 27, 13–39 3, 14–16 24, 16–39 7 16,21,24,29,32,34,39 and 3 21,24,34 studies were included for the outcomes of cognitive impairment, MCI, dementia, AD and VD in meta‐analysis respectively, meanwhile, 12, 2, 9, 3 and 2 studies were included in network meta‐analysis respectively. Supplement Figure presents the bias and overall risk diagrams of the enroled studies.…”

Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta‐analysis

“…Percentage of men ranged from 38.2 to 98.9. Twenty-two studies were cohorts, [113][114][115][116][117][118][119][120][121]124,125,[128][129][130][131][132][133][134][135][136][137]139 four were nested casecontrols 122,123,127,138 and one was a case-control study. 126 Median follow-up duration ranged from 3.1 to 12.4 years.…”