Canagliflozin Reduces All-cause Hospitalization in Patients with Type 2 Diabetes Mellitus

Background: Canagliflozin has been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease. Objective: We investigated the impact of canagliflozin on all-cause hospitalizations (ACH). Methods: Participant-level data was analyzed from the CANVAS Program and CREDENCE trials. Proportional means model was used to compare the mean cumulative function of ACH events over time between canagliflozin and placebo overall (adjusted for baseline estimated glomerular filtration rate [eGFR] strata) and within each stratum of baseline eGFR (<45, 45-60, and >60mL/min/1.73m2). Results: In 14,540 participants during a mean follow-up of 3.3 years, 5031 (34.6%) participants were hospitalized and a total 10,136 ACH were reported. Overall, 1919 (13.2%), 2972 (20.4%), and 9649 (66.4%) participants had eGFR <45, 45-60, and >60mL/min/1.73m2, respectively. When adjusted for eGFR, canagliflozin, compared with placebo, significantly reduced ACH (205.3 versus 235.1 events per 1000 patient-years, respectively; mean number of events ratio [MER] 0.91, 95% confidence interval [CI] 0.87-0.95). Canagliflozin significantly reduced ACH in participants with eGFR <45mL/min/1.73m2 (311.8 versus 407.3 events per 1000 patient-years; MER 0.79, 95% CI 0.71-0.87) and 45-60mL/min/1.73m2 (250.5 versus 297.9 events per 1000 patient- years; MER 0.85, 95% CI 0.78-0.92), but not >60mL/min/1.73m2 (181.9 versus 188.0 events per 1000 patient-years; MER 0.97, 95% CI 0.93-1.03; interaction p <0.0001). Conclusion: ACH was common with over one-third of participants hospitalized during a mean follow-up of 3.3 years. In these analyses, canagliflozin reduced ACH in patients with type 2 diabetes mellitus, with greater absolute and relative effects in those with lower eGFR.