Effects of Canagliflozin on Albuminuria and eGFR Decline Using an Individual Preintervention eGFR Slope

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Background: Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with early stage of chronic kidney disease (CKD). To assess the effect of canagliflozin on kidney function in patients with type 2 diabetes (T2D) and microalbuminuria, we used a novel trial design using the individual’s change in the rate of estimated glomerular filtration rate (eGFR) decline before (preintervention slope) and during treatment (chronic slope). Methods: We conducted a randomized, parallel-group, open-labeled trial (CANPIONE study) at 21 sites in Japan. We randomly assigned (1:1) participants with T2D, urinary albumin-to-creatinine ratio (UACR) of 50 to <300 mg/g, and an eGFR of ≥45 mL/min/1.73m2 to receive 52 weeks of canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope (chronic−preintervention), respectively. The study is registered with the Japan Registry of Clinical Trials (jRCTs061180047). Results: Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was greater in the canagliflozin group than the control group (between-group difference, −30.8% (95%CI −42.6 to −16.8); p=0.0002). The change in eGFR slope (chronic−preintervention) was 1.4 (95%CI −0.6 to 3.3) and −3.1 (95% CI −5.1 to −1.0) mL/min/1.73m2 per year in the canagliflozin and control groups, respectively, resulting in a between-group difference (canagliflozin−control) of 4.4 mL/min/1.73m2 per year (95%CI 1.6 to 7.3, p=0.0022). The effect of canagliflozin in slowing the rate of eGFR decline was more pronounced in participants with steeper preintervention slope than that in slow progressors (5.6 vs. 3.1 mL/min/1.73m2 per year). Conclusion: Canagliflozin reduced albuminuria and the patient-specific eGFR trajectory in patients with T2D and microalbuminuria. The results from the CANPIONE study suggest that the within-individual change in eGFR slope may be a novel approach to identify participants with faster preintervention eGFR decline and to determine the kidney protective potential of new therapies in early stage of CKD. Funding: Commercial Support - Mitsubishi Tanabe Pharma Corporation

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