CREDENCE: Canagliflozin demonstrates CV, renal benefits in type 2 diabetes without CVD

Issue: July 2019

SAN FRANCISCO — Among adults with type 2 diabetes and chronic kidney disease, the SGLT2 inhibitor canagliflozin reduced risk for a cardiovascular event or renal failure regardless of prior history of CV disease, according to new subgroup analyses from the CREDENCE trial presented at the American Diabetes Association Scientific Sessions.

“The CREDENCE trial is the first trial in 18 years to show prevention of renal or cardiovascular outcomes in people with type 2 diabetes and at high risk for progressive chronic kidney disease,” Meg Jardine, MBBS, PhD, conjoint associate professor of medicine at the University of New South Wales in Australia, and program head at the George Institute for Global Health, said during a press conference. “It is the first study to show, for any type 2 diabetes treatment, CV benefit in people who have not previously experienced a CV event — the primary prevention cohort.”

In CREDENCE, researchers randomly assigned 4,401 patients with type 2 diabetes and CKD to placebo or 100 mg canagliflozin (Invokana, Janssen; mean age, 63 years; mean HbA1c, 8.3%; mean diabetes duration, 15.8 years). Primary endpoints of the study were the occurrence of end-stage renal disease, a doubling of serum creatinine, renal death or CV death with a median follow-up of 30 months. The CREDENCE steering committee announced an early stop of the trial in July based on the achievement of prespecified efficacy criteria.

Primary results, presented at International Society of Nephrology’s World Congress of Nephrology Annual Meeting, demonstrated that ESRD, doubling of serum creatinine and renal or CV death occurred in 340 patients who took placebo and in 245 patients who took canagliflozin (HR= 0.7; 30% reduction with canagliflozin). A composite of ESRD, doubling of serum creatinine or renal death occurred in 224 patients who took placebo and in 153 patients who took canagliflozin (HR = 0.66; 34% reduction with canagliflozin).

Among adults with type 2 diabetes and chronic kidney disease, the SGLT2 inhibitor canagliflozin reduced risk for a cardiovascular event or renal failure regardless of prior history of CV disease.

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In the new analyses, researchers found that the observed CV and renal benefits were consistent across different subgroups of patients, including those without pre-existing CVD.

Canagliflozin reduced the risk for the composite of CV death, myocardial infarction and stroke by 32% in the primary prevention group (HR = 0.68; 95% CI, 0.49-0.94) and 15% in the secondary prevention group (HR = 0.85; 95% CI, 0.69-1.06).

“We saw a consistency in effect for all of these outcomes ... regardless of whether or not you experienced a CV event before enrolling,” Jardine said.

Jardine said the researchers also observed a reduction in renal-related adverse events in patients assigned canagliflozin, an important outcome given the high-risk population. – by Regina Schaffer

Reference:

Jardine M, et al. CREDENCE and CARMELINA — Results from two major clinical trials in kidney and cardiovascular disease in diabetes. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco.

Disclosure: Jardine reports she served on the steering committee for the CREDENCE trial, which was sponsored by Janssen.