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SGLT2 Inhibition and Hospitalizations in Patients with CKD: A Meta-Analysis of Kidney Outcome Trials

Oshima, M; Buizen, L; Jongs, N; Levin, A; Chertow, GM; Wheeler, DC; Heerspink, HJL; ... Neuen, BL; + view all (2025) SGLT2 Inhibition and Hospitalizations in Patients with CKD: A Meta-Analysis of Kidney Outcome Trials. Clinical Journal of the American Society of Nephrology 10.2215/CJN.0000000771. (In press).

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Abstract

Background: Unplanned hospitalization, irrespective of cause, is a meaningful outcome for patients, caregivers, clinicians and health systems. The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on all-cause hospitalization in patients with chronic kidney disease (CKD) has not been systematically evaluated. / Methods: We conducted a post-hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial to evaluate the effect of canagliflozin on non-elective all-cause hospitalization using Cox proportional hazards models, with recurrent events analysis to assess effects on first and subsequent hospitalizations. We performed inverse variance weighted meta-analysis of three placebo-controlled SGLT2 inhibitor CKD-focused trials to assess the relative and absolute effects of SGLT2 inhibitors on first and subsequent all-cause hospitalizations overall and across clinically relevant subgroups. For analyses of cause-specific hospitalization, adverse events that were reported by investigators but not adjudicated were used. / Results: Over a median follow-up of 2.6 years, 3015 hospitalizations occurred among 1543 of 4401 (35%) participants in the CREDENCE trial. Compared with placebo, canagliflozin reduced the risk of first all-cause hospitalization (hazarrd ratio [HR] 0.88, 95% confidence interval [CI] 0.80-0.98; p=0.02) and first and subsequent hospitalizations (HR 0.86, 95% CI 0.76-0.96; p=0.007). In a meta-analysis of three placebo-controlled SGLT2 inhibitor CKD-focused trials, SGLT2 inhibitors reduced the risk of first and subsequent hospitalizations from any cause by 15% (HR 0.85, 95% CI 0.78-0.95; p<0.001), with consistent effects irrespective of diabetes, baseline kidney function and albuminuria (all P-interactions >0.50). Reductions were driven by hospitalizations due to infection, cardiac, renal or urinary, and metabolism or nutritional disorders. We estimated that SGLT2 inhibition in CKD would prevent 36 (95% CI 13-56) unplanned hospitalizations per 1000 patient-years of treatment, across a broad range of patients. / Conclusions: SGLT2 inhibitors reduce the risk of hospitalizations from any cause in patients with CKD, irrespective of diabetes status, kidney function and degree of albuminuria.

Type: Article
Title: SGLT2 Inhibition and Hospitalizations in Patients with CKD: A Meta-Analysis of Kidney Outcome Trials
Location: United States
DOI: 10.2215/CJN.0000000771
Publisher version: https://doi.org/10.2215/cjn.0000000771
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10211921
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