Secondary analyses of data from the landmark CREDENCE trial show that the protective renal benefits of the SGLT2 inhibitor canagliflozin are greatest among type 2 diabetes patients with lower kidney function.
Although it was a nephrology meeting, you might have been forgiven if you thought you walked into a diabetes meeting. That’s understandable, considering that nephrologists and researchers are still poring over secondary analyses from landmark studies that show how the class of type 2 diabetes (T2D) drugs—sodium glucose co-transporter 2 (SGLT2) inhibitors—are changing kidney care as well.
The effect and safety of these newer drugs on kidney function were highlighted in posters and oral reports presented last weekend at the American Society of Nephrology's (ASN) Kidney Week 2019.
People with diabetes are twice as likely as people without diabetes likely to develop chronic kidney disease (CKD) and at least 6 times more likely to develop end-stage renal disease (ESRD), one of the most debilitating conditions for patients and one of the costliest for the health system.
In September, canagliflozin, the first of the SGLT2 inhibitors approved in 2013 for type 2 diabetes (T2D), received FDA approval to treat diabetic kidney disease and to reduce the risk of hospitalization for heart failure for the roughly 1 in 3 patients with T2D with renal disease. The CREDENCE study, presented in April, showed that canagliflozin reduced the risk of renal failure or death by 30% in this population. Canagliflozin, like other drugs in its class, works by shipping excess blood sugar out of the body through urine. The approved competitors in the class, empagliflozin and dapagliflozin, are both being studied in renal outcomes trials now under way, EMPA-KIDNEY and Dapa-CKD.
Here is a look at some of the reports from Kidney Week:
Renal, Cardiovascular, and Safety Outcomes of Canagliflozin (CANA) According to Baseline Kidney Function: A CREDENCE Secondary Analysis
This study assessed canagliflozin’s efficacy and safety according to a lower level of estimated glomerular filtration rate (eGFR), a measure of kidney function, than its current label, which is eGFR ≥45ml/min per 1.73 m2, or those with moderate declines in kidney function.1 However, this study showed that the most renal benefit was observed in people with even lower kidney function.
The CREDENCE study enrolled 4401 participants with eGFR 30-<90ml/min per 1.73 m2 and urinary albumin:creatinine ratio >300-5000mg/g, randomizing them within eGFR-based strata to canaglifozin 100 mg daily or matching placebo.
In this secondary analysis, primary and prespecified secondary composites and safety outcomes were analyzed using Cox proportional hazards regression within each screening eGFR stratum: 30-<45, 45-<60 and 60-<90ml/min per 1.73m2.
At screening, 1313 participants fell into 3 stages:
Overall, canaglifozin reduced the primary outcome, the renal composite of end-stage kidney disease, doubled serum creatinine, reduced the risk of dialysis, transplantation or death, had a range of positive cardiovascular outcomes and fewer serious adverse events with no impact on fractures or amputations.
The benefits of canaglifozin were individually significant in people with a screening eGFR 30-<45ml/min per 1.73 m2 for the primary composite, renal composite and composite of CV death or hospitalization for heart failure (95% CI upper limit <1.00). Canaglifozin safely reduced the risk of renal and CV events in people with T2D and substantial albuminuria, and these benefits are preserved across a spectrum of eGFR 30-<90ml/min per 1.73m 2.
Canagliflozin and Renal-Related Adverse Events in Type 2 Diabetes and CKD: Results from CREDENCE
Another analysis using CREDENCE data examined the incidence of renal-related adverse events (AEs) during treatment with canagliflozin.
Rates of renal-related AEs were analyzed using an on-treatment approach overall and by screening eGFR strata (30-<45, 45-<60, and 60-<90 ml/min per 1.73 m2).
The incidence rate of renal-related AEs was lower with canagliflozin versus placebo; there were consistent results for the majority of specific AEs, including acute kidney injury, azotemia, blood creatinine increased, glomerular filtration rate decreased, nephropathy toxic, renal failure, and renal impairment.
The incidence rate for serious renal-related AEs was also lower with canagliflozin and the incidence rates of renal-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata.
Renal-related serious AEs were also lower with canagliflozin relative to placebo across the 3 eGFR strata.