Canagliflozin (Invokana, Janssen) improved renal outcomes and demonstrated potential renal protective effects in patients with type-2 diabetes mellitus (T2DM) who have heart disease or are at risk for it, new analyses from the CANVAS clinical trial program show. The data were presented at the American Society of Nephrology Kidney Week 2017 Annual Meeting on November 3 in New Orleans.
The renal analyses showed that compared to placebo, canagliflozin reduced the risk of kidney disease progression, including significantly reducing urinary albumin excretion and stabilizing estimated glomerular filtration rate (eGFR) over a study duration of more than six years:
- Canagliflozin reduced the rates of several prespecified major renal composite endpoints by up to 47%, such as end-stage kidney disease (ESKD), doubled serum creatinine (dSCr), or renal death (95% confidence interval [CI], 33%–84%).
- Urinary albumin excretion was 18% lower in all participants treated with canagliflozin compared with placebo (95% CI, 16%–20%). It was 34% lower (95% CI, 29%–38%) in participants with baseline microalbuminuria and 36% lower (95% CI, 28%–43%) in those participants with baseline macroalbuminuria. Median urinary albumin to creatinine ratio was 12.3 mg/g.
- Participants treated with canagliflozin experienced an initial decline in mean eGFR; thereafter, that rate gradually increased over the study duration (6.5 years). In contrast, participants treated with placebo experienced a progressive decline in eGFR. Mean baseline eGFR was 76.5 mL/min/1.73 m2.
- There was no increase in renal adverse events (serious or nonserious) compared to placebo, including acute kidney injury and hyperkalemia.
Canagliflozin demonstrated consistent improvement of renal outcomes across multiple composite endpoints that were independently confirmed by an Endpoints Adjudication Committee.
The CANVAS Program is the longest, largest, and broadest completed cardiovascular (CV) outcomes program of any sodium glucose cotransporter 2 (SGLT2) inhibitor, to date, and was the first program to assess the efficacy, safety, and durability of canagliflozin in more than 10,000 patients with T2DM who had either a prior history of CV disease or at least two CV risk factors.
The data from the integrated analysis of the CANVAS and CANVAS-R trials were presented earlier this year in a symposium at the American Diabetes Association 77th Scientific Sessions on June 12 in San Diego, and simultaneously published in the New England Journal of Medicine. The results from the integrated analysis showed canagliflozin significantly reduced the combined risk of CV death, myocardial infarction (MI), and nonfatal stroke versus placebo in patients with T2DM at risk for, or with a history of, CV disease. Additional analysis revealed canagliflozin treatment was associated with a reduced risk for hospitalization for heart failure and demonstrated potential renal protective effects.
In the randomized, placebo-controlled phase 3/4 studies of the CANVAS Program, a vast majority of patients were obese, with a history of hypertension, 66% of patients had a history of CV disease (14% had a history of heart failure), and 34% of patients had at least two CV risk factors. The study assessed the safety of canagliflozin relative to placebo in patients receiving specific commonly-used diabetes agents. The primary endpoint was defined as major adverse CV events (MACE), composed of nonfatal MI, nonfatal stroke, and CV death, and the secondary endpoint was defined as progression of albuminuria, beta-cell function, eGFR changes and UACR.
Source: Janssen Research & Development; November 3, 2017.