The American Diabetes Association (ADA) has made important changes to its 2019 Standards of Care based on findings from the CREDENCE (Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy) trial, which were published in April in the New England Journal of Medicine.

In CREDENCE, investigators randomly assigned 4401 patients with diabetic nephropathy (urinary albumin to creatinine ratio greater than 300 mg/g and estimated glomerular filtration rate [eGFR] 30 to less than 90 mL/min/1.73 m2) to receive the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (100 mg daily) or placebo. Interim results showed that canagliflozin users had a 30% lower composite risk of end-stage renal disease (ESRD), doubling of serum creatinine, or death from renal or cardiovascular causes. The composite renal risk of ESRD, doubling of serum creatinine, and death from renal causes was lower by 34% with treatment.

According to the ADA update, clinicians should:  

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  • Assess urinary albumin (e.g., spot urinary albumin-to-creatinine ratio) and estimated glomerular filtration rate at least once a year in all patients with type 2 diabetes and type 1 diabetes patients with duration of 5 or more years.
  • Consider use of a SGLT2 inhibitor in type 2 diabetes patients with diabetic nephropathy who have an eGFR of 30 mL/min/1.73 m2 or higher and have albuminuria exceeding 300 mg/g to reduce the risk of kidney disease progression and cardiovascular events.
  • Consider use of a glucagon-like peptide 1 receptor agonist to reduce the risk of albuminuria progression and cardiovascular events in patients with chronic kidney disease (CKD).
  • Skip previous recommendations for microvascular complications and foot care, which have been removed after CREDENCE.

According to ADA, the risk-benefit profile of SGLT-2 inhibitor treatment appears favorable for most patients with type 2 diabetes and CKD. An increased risk for diabetic ketoacidosis (DKA) was noted with canagliflozin, but no increased risks for lower-limb amputations, fractures, acute kidney injury, or hyperkalemia.

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American Diabetes Association. 10. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes—2019 [web annotation]. Diabetes Care 2019;42(Suppl. 1):S103–S123.

Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019. doi:10.1056/NEJMoa1811744