Canagliflozin Reduces Risks Even at Lower eGFR Levels

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In patients with type 2 diabetes, canagliflozin has cardiovascular and renal benefits even at lower levels of kidney function, according to an analysis of clinical trial data reported in Circulation.

The analysis included data on 10,142 patients with type 2 diabetes and high cardiovascular risk enrolled in the industry-sponsored “Canagliflozin Cardiovascular Assessment Study” (CANVAS). Patients were randomly assigned to treatments with canagliflozin, a sodium-glucose co-transporter 2 inhibitor, or placebo. About 20% of patients had CKD, defined as a baseline eGFR of less than 60 mL/min/1.73 m2. Of this group, about 72% had a history of cardiovascular disease. Estimated glomerular filtration rate was less than 45 mL/min/1.73 m2 in 5.5% of patients; the trial excluded patients with eGFR less than 30 mL/min/1.73 m2.

The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke. This and secondary outcomes were assessed in patients with and without CKD, and at different levels of baseline eGFR.

At all eGFR levels, canagliflozin reduced HbA1c, systolic blood pressure, body weight, and albuminuria, compared to placebo. The HbA1c-lowering effect was attenuated at lower eGFR levels. There was a significant reduction in the composite outcome with canagliflozin: hazard ratio 0.86. This benefit remained significant in patients with versus without CKD and in all kidney function subgroups, including those with eGFR less than 45 mL/min/1.73 m2. The effect on fatal/nonfatal stroke was “possibly greater” in patients with lower levels of kidney function.

Canagliflozin was also associated with a reduced risk of kidney disease progression (sustained 40% reduction in eGFR, development of ESRD, or death from renal causes). The overall hazard ratio for reduction in kidney disease progression was 0.60, and was consistent across CKD and eGFR groups. Safety outcomes and absolute risk reductions were also similar between groups.

Previous results have suggested that canagliflozin can reduce cardiovascular events and mortality in high-risk patients with type 2 diabetes. Because its blood sugar-lowering effects depend on kidney function, canagliflozin is not currently approved for patients with eGFR 45 under mL/min/1.73 m2.

Secondary analysis of CANVAS data suggests that the cardiovascular and renal benefits of canagliflozin extend to type 2 diabetics down to an eGFR of 30 mL/min/1.73 m2. The researchers conclude: “Reassessing current limitations on the use of canagliflozin in CKD may allow additional individuals to benefit from this therapy” [Perkovic V, et al. Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function. Circulation 2018; 0:CIRCULATIONAHA.118.035901].