The American Diabetes Association (ADA) issued updates earlier this month to its 2019 Standards of Medical Care in Diabetes based on findings from the CREDENCE (Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy) trial.
The trial, which was funded by Janssen and published April 14 by the New England Journal of Medicine, looked at the effect of canagliflozin therapy on cardiorenal outcomes in patients with diabetes-related chronic kidney disease (CKD). CREDENCE included 4,401 patients with type 2 diabetes, an estimated glomerular filtration rate (GFR) of 30 to below 90 mL/min/1.73 m2, and albuminuria who were treated with renin-angiotensin system blockade and randomized to 100 mg of canagliflozin or placebo daily.
The group taking canagliflozin, an oral sodium-glucose cotransporter-2 (SGLT2) inhibitor, had a 30% lower relative risk for the study's primary outcome, a composite of end-stage kidney disease, doubling of serum creatinine level, or death from renal or cardiovascular (CV) causes. Relative risk for the composite renal outcome (end-stage kidney disease, doubling of creatinine level, or death from renal causes) was 34% lower in the canagliflozin group, and relative risk for end-stage kidney disease was 32% lower. Rates of amputation and fracture were similar in both groups, but those in the canagliflozin group had a higher risk for diabetic ketoacidosis. The CREDENCE trial was stopped early after a planned interim analysis.
On June 3, the ADA updated Section 10, Cardiovascular Disease and Risk Management, and Section 11, Microvascular Complications and Foot Care, in the 2019 Standards of Medical Care in Diabetes. (Of note, the American College of Cardiology endorses Section 10 and also reviewed and approved the Section 10 updates.)
Based on the results of CREDENCE, the evidence ratings for use of an SGLT2 inhibitor versus a glucagon-like peptide-1 (GLP-1) receptor agonist have been differentiated. A Grade A recommendation now states that clinicians should consider using a SGLT2 inhibitor in patients with an estimated GFR of 30 mL/min/1.73 m2 or greater, particularly those with albuminuria above 300 mg/g, to reduce risk for CV disease progression, CV events, or both. In patients with CKD who are at increased risk for CV events, the ADA noted that use of a GLP-1 receptor agonist may reduce risk for progression of albuminuria, CV events, or both. This is a Grade C recommendation.
The ADA recommends that urinary albumin and estimated GFR be assessed at least once yearly in all patients with type 2 diabetes, regardless of treatment, as well as in patients with type 1 diabetes of at least five years' duration and all patients with comorbid hypertension. This is a Grade B recommendation. The ADA no longer recommends continued monitoring of urinary albumin-creatinine ratio to assess response to treatment or progression of CKD in patients with albuminuria who are being treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.
The updated 2019 Standards of Medical Care in Patients with Diabetes are available on the Diabetes Care website.