Empagliflozin decreases the risk for chronic kidney disease (CKD) progression in patients who have an estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) as low as 20, according to new trial findings presented at the American Society of Nephrology’s Kidney Week 2022 conference in Orlando, Florida, and simultaneously published in the New England Journal of Medicine. Another study presented at the conference found that kidney function declines more slowly in patients with type 2 diabetes who use a sodium-glucose cotransporter 2 inhibitor (SGLT2i), such as empagliflozin, rather than a dipeptidyl peptidase-4 inhibitor (DPP4i).
In the New England Journal of Medicine trial, investigators from The EMPA-KIDNEY Collaborative Group randomly assigned 6609 patients with an eGFR of 20 to less than 45 or an eGFR of 45 to 90 with a urinary albumin-to-creatinine ratio (UACR) of at least 200 mg/g to receive empagliflozin (10 mg once daily) or matching placebo. During a median 2.0 years, CKD progression or death from cardiovascular causes occurred in 13.1% of the empagliflozin group and 16.9% of the placebo group, with the empagliflozin group experiencing a significant 28% decreased risk for the endpoint, the investigators reported. CKD progression was defined as end-stage kidney disease, a sustained decrease in eGFR of 40% or more or an eGFR less than 10, or death from renal causes. Diabetes status did not affect results.
The risk for all-cause hospitalization also was a significant 14% lower for the empagliflozin group, the team reported. Rates of serious adverse events were comparable.
“Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo,” the investigators concluded.
Ofri Mosenzon, MD, MSc, of Hadassah Medical Center in Jerusalem, Israel, and colleagues found that empagliflozin also benefits patients with diabetes. Using the 2015-2021 Maccabi Healthcare Services database, the investigators propensity-score matched in a 1:1 ratio, by 96 baseline characteristics, 15,992 patients with type 2 diabetes who were new users of empagliflozin or a DPP4i.
Mean eGFR declined more slowly per year with empagliflozin vs DPP4i treatment: -1.33 vs -2.26 mL/min/1.73 m2 per year, Dr Mosenzon reported on behalf of his team. The eGFR slope became gentler with longer empagliflozin use. The investigators found similar results when comparing any SGLT2i to DPP4i.
Compared with DPP4i, long-term use of empagliflozin or any SGLT2i is associated with mitigation of kidney function loss in the general type 2 diabetes population, Dr Mosenzon’s team concluded. The study findings complement data from randomized controlled trials showing that SGLT2i use mitigates kidney function loss in patients with type 2 diabetes at high cardiovascular and kidney risk.
Disclosure: The New England Journal of Medicine study was supported by Boehringer Ingelheim and others. The diabetes study also received commercial support. Please see the original references for a full list of disclosures.
Herrington, Staplin, Landray, Baigent, Haynes et al; EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Eng J Med. Published online November 4, 2022. doi:10.1056/NEJMoa2204233
Mosenzon O, Melzer C, Yanuv I, et al. Long-term use of empagliflozin vs. DPP4 inhibitors mitigates eGFR slopes in patients with type 2 diabetes: real-world evidence. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Abstract SA-PO266.