麻豆传媒

AUSTIN, Texas -- Canagliflozin (Invokana) can have renoprotective benefits, even among those with earlier-stage chronic kidney disease, researchers reported here.

According to a prespecified renal-outcome analysis of the CANVAS trial program, which previously reported a lowered risk of cardiovascular events in patients with type 2 diabetes with the SGLT-2 inhibitor, the drug lowered the urinary albumin to creatinine ratio (UARC) 17% and 23% from baseline in patients with preserved (eGFR ≥60 mL/min/1.73m²) and reduced kidney function (eGFR <60), respectively.

The analysis, presented at the by Brendon Neuen, MBBS, of the George Institute for Global Health in Sydney, and colleagues, excluded stage 4 and higher kidney disease (eGFR <30 mL/min/1.73 m²).

Patients with both preserved and reduced kidney function were less likely to have the prespecified outcome of a 40% decline in eGFR, end-stage kidney disease or renal death on canagliflozin than placebo (HR 0.53, 95% CI 0.39-0.73, and HR 0.76, 95% CI 0.49-1.17, P=0.28 for heterogeneity).

Additionally, both groups also saw similar outcomes in a composite endpoint of doubling of serum creatinine, end-stage kidney disease or renal death (HR 0.42, 95% CI 0.23-0.75, and HR 0.81, 95% CI 0.37-1.77, P=0.21 for heterogeneity).

"The effects of canagliflozin on slowing kidney disease progression are significant, regardless of kidney function and consistent with data from other SGLT-2 inhibitors," co-author George Bakris, MD, of the University of Chicago Medicine, told to 麻豆传媒. He added these data "provide hope" there will be positive outcomes seen with canagliflozin treatment in the ongoing -- the first renal outcome trial with a specific primary composite endpoint evaluating an SGLT-2 inhibitor in patients with diabetic kidney disease, whose results are expected in 2019.

Following the positive findings from the original CANVAS-Renal outcome trial, which yielded similar outcomes to the EMPA-REG trial evaluating empagliflozin (Jardiance), Bakris added that the CREDENCE trial was one reason behind wanting to conduct the current analysis.

"Given that the CREDENCE trial is ongoing and is statistically powered for a primary renal outcome study using canagliflozin we wanted to take a deeper look at the renal data from CANVAS to provide greater insight as to what the possible renal outcomes and safety profile may be at trial end of CREDENCE," he noted.

Other benefits of canagliflozin reported in the analysis included a significant reduction in HbA1c and body weight, in line what has been seen in prior studies, for both patients with preserved and reduced kidney function:

• HbA1c: -0.64% and -0.43%, respectively
• Body weight: -1.43 kg (3.15 lbs) and -1.16 kg (2.56 lbs), respectively

In regards to safety, both preserved and reduced kidney function groups favored canagliflozin for a lowered risk of serious renal-related adverse events (HR 0.70, 95% CI 0.38-1.26, and HR 0.91, 95% CI 0.47-1.74) and serious acute kidney injury (HR 0.60, 95% CI 0.30-1.21, and HR 0.78, 95% CI 0.35-1.73).

However, those with reduced kidney function saw a higher risk of serious hyperkalemia (HR 2.11, 95% CI 0.42-10.60) compared to preserved function (HR 0.26, 95% CI 0.05-1.40).

Both groups saw an elevated risk fracture and amputations, reflective of the primary CANVAS program trial finding that prompted the FDA to require canagliflozin to carry a boxed warning on the product label.

Comment