ADA 2019 Highlights: Primary And secondary Prevention Outcomes From CREDENCE

The CREDENCE trial, first of its kind with dedicated renal outcomes of Canaglifozin for patients with Type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) made highlights in the diabetes community due to its results demonstrating a 30% lower relative risk of composite of end-stage kidney disease (ESKD), doubling of the serum creatinine level, or death from renal or cardiovascular causes.

The results of this multinational, randomized, double-blind, placebo-controlled trial were published in April 2019 in the New England Journal of Medicine and this evidence prompted the American Diabetes Association (ADA) to update their clinical practice guidelines to “Consider using a Sodium-glucose co-transporter 2 (SGLT2) inhibitor when the estimated glomerular filtration rate (eGFR) is at or above 30 mL/minute/1.73 m², especially with albuminuria above 300 mg/g, to reduce the risk of CKD progression, cardiovascular events, or both” (Grade of evidence: A).

The CREDENCE outcomes came as a big win for patients with T2DM and CKD, considering the high risk of renal failure in this group, and the magnitude of benefit that Canagliflozin provided in reducing the cardiovascular (CV) and renal adverse events.

Primary and secondary prevention subgroup analysis

This week, CREDENCE once again made highlights at ADA 79^th Scientific sessions 2019 held in San Francisco, USA when the investigators revealed a subgroup analysis of the cardiovascular (CV) and renal outcomes for patients with no history of cardiovascular disease (CVD) (primary prevention cohort, n=2181, 49.6%) and those with a history of coronary, cerebrovascular, or peripheral vascular disease (secondary prevention cohort, n= 2220, 50.5%).

Cardiovascular outcomes

The following results revealed the ability of Canagliflozin to significantly reduce the risk of adverse CV outcomes in both the primary and secondary prevention cohort when compared with placebo:

• Reduction in CV death or hHF: 26% and 34% in the primary and secondary cohort, respectively
• Reduction in a composite of CV death, myocardial infarction or stroke: 32% and 15% in the primary and secondary cohort, respectively
• Reduction in CV death: 25% and 21% in the primary and secondary cohort, respectively

Renal outcomes

The results were also presented for the renal outcomes of Canagliflozin treatment which revealed a 32% and 36% reduction in renal specific composite outcome in the primary and secondary prevention groups, respectively when compared to placebo. Canagliflozin also reduced the risk of the composite outcome of dialysis, kidney transplantation, or renal death by 35% in the primary prevention group and by 17% in the secondary prevention group.

In line with the results of previous studies for Canagliflozin, CREDENCE outcomes demonstrated a placebo comparative safety profile of Canagliflozin with no increase in the risk of lower-limb amputations, fractures, acute kidney injury, or hyperkalemia.

The initial CREDENCE results and the recent deep-dive into the CV and renal outcomes have made Canagliflozin the first anti-diabetic to offer CV benefit in patients without a history of CVD and has opened new vistas for utilizing its protective benefits in patients with T2DM and CKD.

1. Perkovic V et.al, Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy, N Engl J Med.2019 Apr 14. doi: 10.1056/NEJMoa1811744.


2. ADA Standards Updated With Renal Guidance Based on CREDENCE – Medscape – Jun 04, 2019.


3. INVOKANA® (canagliflozin) Significantly Reduced Major Cardiovascular Events and Kidney Failure in Patients with Type 2 Diabetes and Chronic Kidney Disease in New CREDENCE Analysis. News provided by Janssen Pharmaceutical Companies of Johnson & Johnson. Jun 11, 2019, 12:30 ET. Available at: https://www.prnewswire.com/news-releases/invokana-canagliflozin-significantly-reduced-major-cardiovascular-events-and-kidney-failure-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-in-new-credence-analysis-300865507.html