Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown a wide range of benefits among those with cardiovascular (CV) disease, diabetes mellitus (DM), and chronic kidney disease (CKD). The CREDENCE trial found that canagliflozin lowered risk of kidney failure and adverse CV events in patients with concurrent CKD and type 2 DM.¹ DAPA-CKD found similar results with dapagliflozin in CKD patients both with and without DM.² Notably, CREDENCE and DAPA-CKD studies excluded patients with glomerular filtration rates (GFRs) less than 25 or 30 mL/min/1.73m² respectively and only included those with an elevated urine albumin-to-creatinine ratio (ACR).

To address this gap, the randomized, double-blind, placebo-controlled EMPA-KIDNEY trial examined the effect of empagliflozin on patients with GFR between 20 to 45 with any ACR and those with a GFR between 45 to 90 with an ACR of at least 200.³ The study randomized 6,609 patients to either empagliflozin 10mg once daily or placebo. At 2-year median follow-up, those treated with empagliflozin experienced significantly lower rates of CKD progression and death from CV causes compared to the placebo group (13.1% vs. 16.9% respectively; hazard ratio [HR] 0.72 [0.64 to 0.82], p<0.001). These findings persisted across all CKD levels and among patients with and without DM. Notably, empagliflozin also led to a lower rate of hospitalization from any cause compared to placebo, although there were no significant differences in the composite outcome of heart failure hospitalizations and death from CV causes.

Empagliflozin use led to a 28% lower risk of CKD progression or death from CV causes across a range of kidney function and among those with and without DM. EMPA-KIDNEY adds to existing evidence for the benefit of SGLT2 inhibitors in slowing the progression of CKD. The study is strengthened by its broad eligibility criteria, which suggests that empagliflozin may also be beneficial in patients with GFR <30 or those with a low ACR.

References

1. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295-2306.
2. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020;383:1436-46.
3. Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2023;388:117-27.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism

Keywords: AHA Annual Scientific Sessions, AHA22, Primary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Canagliflozin, Sodium-Glucose Transporter 2, Diabetes Mellitus, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Creatinine, Follow-Up Studies, Cardiovascular Diseases, Renal Insufficiency, Chronic, Kidney, Hospitalization, Glucose, Albumins, Sodium

< Back to Listings