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

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.