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Evaluation

Oral Presentation

Session: Surprising Benefits of Diabetes Drugs

Risk of kidney stones following SGLT2i- and GLP1-RA initiation among patients with type 2 diabetes in Denmark, Norway, UK, and Taiwan: Population-based active comparator, new user cohort studies and meta-analysis

Wednesday, August 28, 2024
2:30 PM – 2:45 PM CEST
Location: Room II

    Co-Author(s)

  • Lars Christian Lund, PhD (he/him/his)

    Postdoctoral researcher
    Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark
    Odense C, Denmark

  • Shahab Abtahi, MD, PhD

    Assistant Professor
    Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University
    Utrecht University
    Utrecht, Netherlands

  • HL

    Hanne L. Løvdal Gulseth

    Norwegian Institute of Public Health
    Oslo, Norway

  • 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)

  • PL

    Paz Lopez-Doriga Ruiz

    Norwegian Institute of Public Health, Norway

  • Patrick C. Souverein, PhD (he/him/his)

    Assistent professor
    Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University
    Utrecht, Netherlands

  • Adrian Martinez de la Torre, PhD

    Postdoctoral Researcher
    Pharmacoepidemiology Group, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich
    Zurich, Switzerland

  • Andrea Michelle Burden, PhD

    Professor
    Swiss Fenderal Institute of Technology
    Zurich, Switzerland

  • Øystein Karlstad, MscPharm, PhD

    Senior researcher
    Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway.
    Oslo, Norway

  • Olaf H. Klungel, PharmD, PhD

    Head of Division
    Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University
    Utrecht, Netherlands

  • 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)

    • Presenting Author(s)

  • Anton Pottegård, PhD, DMSc

    Professor
    University of Southern Denmark
    Odense M, Denmark

    Slides Handouts
Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have previously been associated with a reduced risk of nephrolithiasis (kidney stones), however, large-scale real-world evidence has been lacking.

Objectives: To conduct a multi-national cohort study to evaluate the association between SGLT2i use and reduced risk of nephrolithiasis.

Methods: We conducted active comparator new user cohort studies in Denmark (2007-2022), Norway (2009-2022), IQVIA Medical Research Database (IMRD; 2016-2021) in the UK (incorporating THIN, a Cegedim database), and Taiwan (2016-2020) using a common protocol. We included all initiators of SGLT2i and glucagon-like peptide 1 receptor agonists (GLP1-RA) who received a prescription for metformin during the year prior to drug initiation and were 40 years of age or older. Cohorts were stratified on whether individuals had a history of nephrolithiasis or not. The outcome of interest was a new hospital diagnosis of nephrolithiasis. To mitigate confounding, we estimated propensity scores based on a priori chosen markers of diabetes severity and prognostic factors of developing nephrolithiasis. We obtained standardised mortality ratio weighted hazard ratios (HR) with robust 95% compatibility intervals (CI) for each site and pooled these using a Bayesian meta-analysis with weakly informative priors. Between-site heterogeneity was quantified using the random-effect (τ), which can be considered negligible if τ < 0.10.

Results: Across all sites, we included 553 316 initiators of SGLT2i and 136 563 initiators of GLP1-RA. Of these, 81 808 and 9590 had a previous history of nephrolithiasis. The majority of individuals were included in the Taiwanese database (56%), with 20% of individuals being included in Denmark and 12% and 10% in Norway and IMRD. We observed 7868 (1.4%) and 1600 (1.2%) incident nephrolithiasis events in the respective groups, yielding a weighted HR of 0.60 (95% CI 0.40–0.94, τ=0.30). Site-specific HRs were comparable across Denmark, Norway and IMRD (HR 0.51, 0.59 and 0.43), while the observed preventive effect was weaker in the Taiwanese population (HR 0.81, 95% CI 0.72–0.90). Results among individuals with a history of nephrolithiasis (weighted HR 0.69, 95% CI 0.45–1.00, τ=0.27) were comparable to those among individuals without prior nephrolithiasis.

Conclusions: We found consistent evidence of a protective effect of SGLT2i on the occurrence of nephrolithiasis, both among individuals with and without a history of nephrolithiasis. Randomized controlled trials are needed to quantify the magnitude of this preventive effect.