Physicians' Academy for Cardiovascular Education

SGLT2 inhibitor improves CV and renal outcomes in diabetic patients with chronic kidney disease

Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function: Data from the CANVAS Program

Literature - Neuen BL, Ohkuma T, Neal B, et al. - Circulation 2018; published online ahead of print

Introduction and methods

Sodium glucose co-transporter 2 (SGLT2) inhibitors are associated with improvements in glycemic status, blood pressure, weight, and proteinuria in patients with type 2 diabetes (T2DM) [1]. However, SGLT2 inhibitors are not recommended for T2DM patients with impaired kidney function [2].

In this post hoc analysis of the CANagliflozin cardio Vascular Assessment Study Program (CANVAS) [3], the effect of the SGLT2 inhibitor canagliflozin on CV, renal, and safety outcomes was assessed, in patients with T2DM at high CV risk and chronic kidney disease (CKD) at different levels of kidney function, including those for whom canagliflozin is currently not approved (estimated glomerular filtration rate [eGFR]: 30-45 mL/min/1.73m2).

The CANVAS Program included two double-blind, placebo-controlled, randomized trials (CANVAS and CANVAS-R) that evaluated the CV and renal safety and efficacy of canagliflozin in T2DM patients with established CVD or at high CV risk. Patients with eGFR <30 mL/min/1.73m2 were excluded from the study. Patients were randomized to receive either canagliflozin 100-300 mg daily, or placebo.

The primary endpoint was the composite of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke. The main renal endpoint was the composite of end-stage kidney disease, renal death, and a 40% decrease in eGFR, or a doubling of serum creatinine. The mean follow-up was 188.2 weeks. Analyses were done using eGFR categories of <45, 45-<60, 60-<90, ≥90 mL/min/1.73m2.

Main results


In T2DM patients with established CVD or at high CV risk and CKD, canagliflozin consistently improved renal and CV outcomes across different levels of kidney function down to eGFR 30 mL/min/1.73m2 . Current eGFR-based limitations may be reconsidered for prescription of canagliflozin to those with impaired kidney function.


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