The cardiovascular and renal effects of the sodium glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin are consistent across different levels of kidney function in people with type 2 diabetes who have or are at high risk of cardiovascular disease, according to a study published in Circulation.

For the study, Brendon L. Neuen, MBBS, et al., conducted a secondary analysis of the CANVAS trial, analyzing the effects of canagliflozin on cardiovascular, renal and safety outcomes in participants with and without chronic kidney disease (CKD) (defined as <60 and ≥60 mL/min/1.73m²) and for all outcomes using four categories for estimated glomerular filtration rate (eGFR) (<45, 45-<60, 60-<90, and ≥90 mL/min/1.73 m²). The CANVAS trial enrolled 10,142 participants with type 2 diabetes and high cardiovascular risk who were followed for a mean of 188 weeks. At baseline, 2,039 participants (20.1 percent) had CKD. Of the patients with CKD, 71.6 percent had a history of cardiovascular disease.

According to the results, the risk reduction in the primary outcome was similar across the four eGFR categories and for participants with and without CKD. The overall effect of canagliflozin on fatal and nonfatal myocardial infraction and hospitalization for heart failure were consistent across the four eGFR categories; however, heterogeneity was observed for the effect on fatal and nonfatal stroke. The same effect was observed for participants with and without CKD. In terms of renal outcomes, using eGFR as a continuous variable, the renoprotective effect of canagliflozin suggested a benefit at all levels of kidney function. In addition, the effects of canagliflozin on safety outcomes were consistent across all eGFR categories.

According to the authors, the relative effects of canagliflozin on most cardiovascular outcomes were consistent across different levels of kidney function, with the exception of heterogeneity for fatal and nonfatal stroke. The researchers concluded that approval of canagliflozin for patients with CKD “may allow additional individuals to benefit from this therapy.”

Keywords: Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Cardiovascular Diseases, Renal Insufficiency, Chronic, Kidney, Stroke, Heart Failure, Sodium-Glucose Transport Proteins

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