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Spotlight Session - RWE Collaborative

Session: Spotlight Poster Session B

(BSPOT47) The Effect of Sodium Glucose Cotransporter-2 Inhibitors on HbA1c Variability and Acute Kidney Injury: A Causal Mediation Analysis

Tuesday, August 27, 2024
8:00 AM – 6:00 PM CEST
Location: Foyer 3

    Co-Author(s)

  • DJ

    Dongze Ji

    Peking University Health Science Center, China (People's Republic)

  • Tiansheng Wang, PharmD, PhD

    postdoc
    University of North Carolina at Chapel Hill
    Chapel Hill, United States

  • Til Stürmer, MD, PhD (he/him/his)

    Professor
    University of North Carolina at Chapel Hill
    Chapel Hill, United States

  • SI

    Sherin Ismail

    University of North Carolina at Chapel Hill, United States

  • SD

    Shujie Dong

    Peking University Third Hospital, China (People's Republic)

  • PS

    Peng Shen

    Yinzhou District Center for Disease Control and Prevention, China (People's Republic)

  • HL

    Hongbo Lin

    Yinzhou District Center for Disease Control and Prevention, China (People's Republic)

  • LS

    Luwen Shi

    Peking University Health Science Center, China (People's Republic)

  • XG

    Xiaodong Guan

    Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, China (People's Republic)

    • Presenting Author(s)

  • Yang Xu, PhD (he/him/his)

    Assistant Professor
    Peking University Health Science Center
    Beijing, China (People's Republic)

Background: The role of lower variability of HbA1c (glycated hemoglobin A1c) in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear.

Objectives: To compare AKI risk between individuals initiating SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i). Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by its effect on reducing long-term HbA1c variability.

Methods:

Design: Active comparator, new-user, observational study
Setting: 19 717 adults with type 2 diabetes in Yinzhou Regional Health Care Database from January 1, 2018, to December 31, 2022, with a median follow-up of 1.76 years.

Exposures or interventions: Initiating SGLT2i (n=6 008) or DPP4i (n=13 709). Covariates include demographic information, comorbidities, comedications, laboratory data, and healthcare utilization.

Main outcome measures: HbA1c reduction, HbA1c variability score (HVS), and AKI.

Statistical analysis: Inverse probability treatment, weighted Cox proportional hazards models, weighted median regression models, and causal mediation analysis.

Results: The adjusted hazard ratio for SGLT2i vs. DPP4i was 0.79 (95% confidence interval [CI] 0.64, 0.98) for AKI. The adjusted differences in median HVS and HbA1c reduction were -16.67% (95% CI: -27.71%, -5.62%) and -1.98% (95% CI: -14.34%, 10.38%), respectively. Furthermore, the reduction in AKI risk associated with SGLT2i was moderately mediated (22.77%) through the treatment effect on HVS. The results remained consistent across various subgroups and sensitivity analyses.

Conclusions: Compared to DPP4i, initiating SGLT2i was associated with a lower risk of AKI, with HbA1c variability mediating the observed reduced AKI risk associated with SGLT2i. These findings underscore the potential mechanisms underlying the protective effect of SGLT2i on AKI compared to DPP4i and highlight the importance of considering HbA1c variability in assessing treatment outcomes.