Kidney protection with canagliflozin: A combined analysis of the randomized CANVAS program and CREDENCE trials

Abstract

Aim: In the CANVAS Program and CREDENCE trials, the sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of cardiovascular and kidney events in patients with type 2 diabetes. The current study analysed a pooled population to ascertain the kidney protection provided by canagliflozin across the full spectrum of kidney parameters.

Methods: This post-hoc pooled analysis of the CANVAS Program (N = 10 142) and CREDENCE trial (N = 4401), assessed the risk of the primary kidney composite (doubling of serum creatinine, end-stage kidney disease, renal death), in all patients and subgroups defined by baseline estimated glomerular filtration rate (<30, 30 to <45, 45 to <60 and ≥60 ml/min/1.73 m² ), albuminuria [<30, 30-300, >300 mg/g (<3.39, 3.39-33.9, >33.9 mg/mmol)] and 2012 Kidney Disease: Improving Global Outcomes (KDIGO) classification of chronic kidney disease (low/moderate, high and very high risk).

Results: In the overall population, the risk for the primary kidney composite outcome was 37% lower in the canagliflozin group versus placebo (HR: 0.63; 95% CI: 0.53, 0.77; p < .001). There was no evidence of heterogeneity in the kidney protective effects of canagliflozin across a range of kidney risks when stratified by baseline estimated glomerular filtration rate, albuminuria or KDIGO risk category (all p_interaction > .05). A statistically significant risk reduction of the primary kidney composite outcome was sustained by approximately 18 months after randomization.

Conclusions: These results emphasize a critical role of canagliflozin in kidney protection across a broad spectrum of participants with type 2 diabetes with varying levels of kidney function.

Keywords: SGLT2 inhibitors; canagliflozin; cardiovascular disease; diabetic nephropathy; type 2 diabetes.