AW-AD-4: RENOPROTECTIVE EFFECTS OF CANAGLIFLOZIN VIA LESSENING HYPERINSULINEMIA IN DIABETIC PATIENTS WITH HEART FAILURE: A POST-HOC ANALYSIS OF THE CANDLE TRIAL

Abstract

Objective: The mechanisms by which sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce proteinuria in patients with type 2 diabetes mellitus (T2DM) remain unclarified. We evaluated factors associated with proteinuria regression in patients with T2DM treated with canagliflozin. Design and method: This study was a post-hoc analysis of the CANDLE trial (UMIN000017669), which compared the effect of 24 weeks treatment canagliflozin and glimepiride for changes in NT-proBNP in patients with T2DM and chronic heart failure (CHF). Factors associated with regression of proteinuria at 24 weeks were evaluated with multivariate logistic models. Results: The rate of regression of proteinuria was higher and that of progression was lower in the canagliflozin versus the glimepiride group. There were no differences in the change in systolic and diastolic blood pressure and eGFR category between groups at baseline. Systolic blood pressure and insulin levels significantly decreased in the canagliflozin group but not in the glimepiride group. Insulin level, HOMA-β, HOMA-IR, and estimated plasma volume were decreased at 24 weeks in the proteinuria regression subclass but not in the proteinuria progression subclass, suggesting that regression of proteinuria is associated with the declines in these values in the canagliflozin group. Systolic and diastolic blood pressure did not change significantly in either the proteinuria progression or regression groups in both the canagliflozin and glimepiride groups. Higher insulin level was solely associated with proteinuria regression in the multivariate logistic regression model. Conclusion: In patients with T2DM and CHF, regression of proteinuria with canagliflozin treatment was associated with the pre-treatment insulin level. These results suggest new mechanistic intuitions into the beneficial effects of canagliflozin on renal outcomes and warrant discussion for selecting preferred patient profiles, including pre-treatment insulin levels.