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CANVAS: Canagliflozin improved renal outcomes in diabetes



Among patients with preserved function at baseline, canagliflozin was associated with a statistically significant 47% decrease in risk of renal death, end-stage kidney disease, or a 40% or greater drop in eGFR (hazard ratio, 0.53; 95% confidence interval, 0.39-0.73). Canagliflozin also showed renal benefits for patients with reduced kidney function, but the effect did not reach statistical significance (HR, 0.76; 95% CI, 0.49-1.17). Findings were similar when the researchers tweaked the composite renal endpoint by replacing the eGFR criterion with doubling of serum creatinine (HR, 0.42; 95% CI, 0.23-0.75 and HR, 0.81; 95% CI, 0.37-1.77, respectively).

Canagliflozin has a black box warning for amputation risk. There was no indication that early renal function further increased this risk, the researchers reported. CANVAS patients who received canagliflozin underwent amputations (usually at the level of the toe or metatarsal) at rates of 6.3 per 1,000 person-years overall, 5.6 per 1,000 person-years in the setting of preserved kidney function, and 9.9 per 1,000 person-years in the setting of reduced kidney function. Rates in the placebo group were 3.4, 3.0, and 4.8 amputations per 1,000 person-years, respectively. Additionally, baseline renal status did not significantly affect risk of fracture, serious kidney-related adverse events, or serious acute kidney injury. Patients with baseline renal insufficiency were at increased risk of developing serious hyperkalemia (HR, 2.11; P = .06), but these events were uncommon in both treatment groups.

No CANVAS patient had stage 4 or worse kidney disease (eGFR less than 30 mL/min per 1.73 m2) at enrollment, the researchers noted. The ongoing phase 3 CREDENCE (Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation) trial will shed more light on canagliflozin in the setting of renal disease, they added. This multicenter, double-blind trial compares canagliflozin with placebo in more than 4,000 patients with diabetic nephropathy. Results are expected in 2019.

Janssen funded the CANVAS and CANVAS-R trials. Disclosures were not provided.

SOURCE: Neuen BL et al. SCM 2018.


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