Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes - 21/02/25

Doi : 10.1016/j.diabet.2025.101623

Mingyang Sun ^a,^{^{†
These authors have contributed equally to this study (joint primary authors).}}, Xiaoling Wang ^a,^b,^{^{†
These authors have contributed equally to this study (joint primary authors).}}, Zhongyuan Lu ^a,^b, Yitian Yang ^a, Shuang Lv ^a, Mengrong Miao ^a, Wan-Ming Chen ^c,^d, Szu-Yuan Wu ^c,^d,^e,^f,^g,^h,^i,^j,^{^{‡
These authors have contributed equally to this study (joint Correspondence authors).},}^⁎ , Jiaqiang Zhang ^a,^k,^{^{‡
These authors have contributed equally to this study (joint Correspondence authors).},}^⁎
^a Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China
^b Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China
^c Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan
^d Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan
^e Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
^f Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
^g Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
^h Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
ⁱ Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
^j Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
^k Institute of Electrophysiology, Henan Academy of Innovations in Medical Science, Zhengzhou, China

^⁎Corresponding authors.No 500, Lioufeng Rd., Wufeng DistrictTaichung City41354Taiwan

Abstract

Background

Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown neuroprotective potential, comparative data on their efficacy in dementia prevention remain scarce.

Methods

- We conducted a retrospective cohort study using the TriNetX database, including 307,103 SGLT2 inhibitor users and 348,686 GLP-1 receptor agonist users with T2DM. Propensity score matching yielded 221,883 pairs with balanced baseline characteristics. The primary outcome was overall dementia incidence, with secondary outcomes including AD, VaD, and all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazards models.

Results

SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89–0.95). The risk of VaD (HR, 0.89; 95 % CI, 0.84–0.95) and AD (HR, 0.90; 95 % CI, 0.86–0.94) was also reduced with SGLT2 inhibitors. All-cause mortality was lower in the SGLT2 group (3.6 % vs. 4.6 %; HR, 0.95; 95 % CI, 0.92–0.98). No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91–1.01).

Conclusions

In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM. These findings support the preferential use of SGLT2 inhibitors in mitigating dementia risk in this population, though randomized controlled trials are warranted for confirmation.

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Keywords : Dementia prevention, GLP-1 receptor agonists, Neuroprotection, SGLT2 inhibitors, Type 2 Diabetes Mellitus

Abbreviations : SGLT2, GLP-1, T2DM, AD, VaD, PSM, HR, CI, HbA1c, BMI, ASMD, ICD, GDPR, HIPAA, ATC, CNS, AMPK, Aβ, FDA, RCT

Plan

Baseline characteristics of patients before and after PSM

Incidence of outcomes among patients treated with SGLT2 inhibitors or GLP-1 receptor agonists

Kaplan–Meier estimates of dementia incidence

Kaplan–Meier estimates of overall survival

Discussion

Conclusions

CRediT authorship contribution statement

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Vol 51 - N° 2

Article 101623- mars 2025 Retour au numéro

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Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes - 21/02/25

Abstract

Background

Methods

Results

Conclusions

Plan

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