SGLT2 Inhibitor Shown to Reduce Renal Death in Type 2 Diabetes

New findings presented at the American Diabetes Association’s 79th Scientific Sessions suggest that the oral sodium-glucose co-transporter-2 (SGLT2) inhibitor dapaglifozin is likely associated with the reduction and prevention of kidney disease progression and renal death in patients with type 2 diabetes with or without atherosclerotic cardiovascular disease (CVD).¹

Until now, the drug has been shown to benefit renal outcomes primarily in patients with established atherosclerotic CVD, the authors of the study wrote.

“Medications like dapagliflozin should also be considered as first line therapy in patients without established [CVD],” said Itamar Raz, MD, professor of internal medicine at Hadassah Medical School at the Hebrew University of Jerusalem and head of the Israel National Council of Diabetes, in a press release. “The drugs have a high safety margin and should be used regularly by primary care physicians,” Dr Raz added.²

Dr Raz and colleagues arrived at their conclusion after conducting the first sub-analysis of renal data from the Dapagliflozin Effect on Cardiovascular Events Thrombolysis In Myocardial Infarction (DECLARE-TIMI 58) trial from April 25, 2013, to September 18, 2018. A total of 17,160 participants were randomly assigned to once-daily 10 mg dapagliflozin or placebo, and mean follow-up lasted 4.2 years.

All participants included in the trial met the following criteria:

• Type 2 diabetes diagnosis.
• Hemoglobin A1c (HbA1c) of 6.5% to 12%.
• Established atherosclerotic CVD or multiple risk factors.
• Creatinine clearance of at least 60 mL/min.

Findings from the study confirmed previous evidence suggesting that dapagliflozin use was associated with a significant reduction in the pre-specified secondary cardiorenal composite outcome compared with placebo (hazard ratio [HR] 0.76), which consisted of

• A continual decrease of at least 40% in estimated glomerular filtration rate (eGFR) to less than 60 mL/min per 1.73m2.
• End-stage renal disease, which the researchers defined as undergoing dialysis for at least 90 days, undergoing kidney transplantation, or having a confirmed sustained eGFR of less than 15mL/min per 1.73 m2.
• Death from renal or cardiovascular causes.

The researchers noted that, excluding death from cardiovascular causes, the HR for the renal-specific outcome was 0.53.

The researchers also observed the following effects among participants treated with dapagliflozin vs placebo:

• A 46% reduction in sustained decline in eGFR by at least 40% to less than 60 mL/min per 1.73 m2 (hazard ratio [HR] 0.54).
• A lower risk of end-stage renal disease or renal death (HR 0.41).
• An improvement in cardiorenal and renal-specific composite outcomes across various pre-specified subgroups, including groups stratified by eGFR at baseline and atherosclerotic CVD status.
• A larger mean decrease in eGFR at 6 months post-randomization.
• An equalized mean change in eGFR at 2 years and lower mean decrease in eGFR at 3 and 4 years compared with placebo.

—Christina Vogt

References:

1. Mosenzon O, Wiviott SD, Cahn A, et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomized trial [Published online June 10, 2019]. Lancet Diabetes Endocrinol. https://doi.org/10.1016/S2213-8587(19)30180-9.
2. Dapagliflozin reduces progression of kidney disease and renal death in people with type 2 diabetes [press release]. San Francisco, CA. https://www.diabetes.org/newsroom/press-releases/2019/dapagliflozin-reduces.html. June 10, 2019. Accessed June 10, 2019.