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Diabetes

Session: Poster Session B

(041) Comparative Protective Effect on Alzheimer Disease between GLP1-RA and SGLT2 Inhibitors

Tuesday, August 27, 2024
8:00 AM – 6:00 PM CEST
Location: Convention Hall II

    Presenting Author(s)

  • Zoe Chi-Jui Chang, PharmD (she/her/hers)

    Research Assistant
    School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Taiwan (Republic of China)

    • Co-Author(s)

  • Miyuki Hsing-Chun Hsieh, PhD

    Immediate Past Chair of the ISPE Student Council
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    Chiayi City, Taiwan (Republic of China)

  • Michael Chun-Yuan Cheng, MA (he/him/his)

    Research Associate
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Taiwan (Republic of China)

  • Edward Chia-Cheng Lai, PhD (he/him/his)

    Professor
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Taiwan
    National Cheng Kung University
    Tainan City, Taiwan (Republic of China)

Background: Previous studies suggested both glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have a protective effect on Alzheimer disease (AD). However, their comparative effect on AD is unknown.

Objectives: We aimed to compare the protective effect on AD between GLP1-RA and SGLT2i in patients with type 2 diabetes (T2D).

Methods: We followed the target trial emulation framework. Our target trials were two head-to-head, open-label, pragmatic randomized controlled trials comparing the risk of AD between GLP1-RA and SGLT2i users with and without insulin treatment respectively. With data between 2016-2020 from the Taiwan National Health Insurance Database, we included adult new users of either GLP1-RA or SGLT2i with type 2 diabetes and excluded patients with neurodegenerative disease histories and contraindications of study drugs. We utilized fine stratification with propensity score to emulate randomization and estimated the average treatment effects (ATE). With Cox proportional hazard model, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) between two study drugs. To test the result robustness, we also conducted two sensitivity analyses with stricter outcomes definitions, and estimated average treatment effect of the treated (ATT).

Results: We identified 350,453 non-insulin users (GLP1-RA, n=19,510; SGLT2i, n= 86,588) and 106,098 insulin users (GLP1-RA, n=12,905; SGLT2i, n= 337,548). Patients' characteristics were balanced between two arms after fine stratification with propensity score. Among patients without insulin use, incidence rate (IR) of AD were 1.41 and 0.94 per 1,000 person-years for GLP1-RA and SGLT2i users, respectively. AD risk was higher in GLP1-RA group compared to SGLT2i users (HR 1.47, 95%CI 1.05- 2.04). Sensitivity analyses yielded HR in consistent direction. Among patients with insulin use, similar risks were observed between two drug groups.

Conclusions: Among T2D patients without insulin use, we found a favorable effect against AD in SGLT2i users compared to GLP1-RA users but not in patients using insulin. The potential effect modification of insulin use in the result warrants further studies.