Empagliflozin, dapagliflozin in a draw for renoprotection in T2D

Long-term kidney outcomes in type 2 diabetes (T2D) are similar between empagliflozin- and dapagliflozin-treated patients, aligning with current clinical practice guidelines that do not favour one SGLT2 inhibitor over the other, according to a study.

In a target trial emulation analysis, the incidence of acute kidney injury during 6 years of follow-up was 18.2 percent with empagliflozin vs 18.5 percent with dapagliflozin (risk ratio [RR], 0.98, 95 percent confidence interval [CI], 0.91–1.06). [JAMA Intern Med 2025;doi:10.1001/jamainternmed.2024.7381]

The same held true for other kidney outcomes. No significant differences between the empagliflozin and dapagliflozin arms were noted for the 6-year incidence of chronic kidney disease stages G3 to G5 among patients with eGFR of ≥60 mL/min/1.73 m² at baseline (11.8 percent vs 12.1 percent; RR, 0.97, 95 percent CI, 0.89–1.05), chronic kidney disease stage A2 or A3 among those without albuminuria at baseline (14.8 percent vs 14.3 percent; RR, 1.04, 95 percent CI, 0.93–1.15), and progression of chronic kidney disease among those with eGFR <60 mL/min/1.73 m² at baseline (5.3 percent vs 5.7 percent; RR, 0.94, 95 percent CI, 0.56–1.58).

Per-protocol analyses yielded the same results.

“The findings do not indicate a kidney advantage of initiating empagliflozin vs dapagliflozin or vice versa as an adjunct therapy in persons with T2D… Given the lack of SGLT2 inhibitor preference in the KDIGO guidelines for T2D management in CKD and the absence of SGLT2 inhibitor recommendations ... for general CKD management, our study provides insights into selecting an appropriate SGLT2 inhibitor for managing these conditions,” the investigators said. [Ann Intern Med 2023;176:381-387; Kidney Int 2024;105:S117-S314]

A total of 32,819 individuals who initiated treatment with empagliflozin and 17,464 who initiated dapagliflozin were included in the analyses. The median age of the entire cohort was 63 years, 37.5 percent were female, and the median eGFR was 88 mL/min/1.73 m².

Class effects

Empagliflozin and dapagliflozin belong to the same drug class, SGLT2 inhibitors, which reduce the risk of cardiovascular and kidney events in T2D patients. The effects of SGLT2 inhibitors are generally considered class effects, with no significant preference for individual agents. However, both European and US guidelines acknowledge the potential for within-class variations. [N Engl J Med 2023;388:117-127; N Engl J Med 2020;383:1436-1446; Circulation 2016;134:752-772; Eur Heart J 2023;44:4043-4140; Diabetologia 2022;65:1925-1966]

“As to our knowledge only one small trial that focused on changes in eGFR has directly compared these agents,” the investigators said. [Diabetes Res Clin Pract 2019;151:65-73]

The open-label trial from South Korea examined the effect of adding empagliflozin vs dapagliflozin to metformin, glimepiride, and dipeptidyl peptidase-4 inhibitor treatment in patients with dysregulated T2D. The changes in eGFR within 52 weeks were similar between the empagliflozin and dapagliflozin groups (−1.2 vs −1.3 mL/min/1.73 m²). Reports from several observational studies likewise showed no significant differences in kidney outcomes between the two drugs. [Diabetes Res Clin Pract 2019;151:65-73; Eur Heart J Cardiovasc Pharmacother 2024;10:432-443; Kidney Int 2022;102:1147-1153]

“In the absence of a large, randomized clinical trial directly comparing kidney outcomes between empagliflozin and dapagliflozin, this emulation of such a target trial provides what is to our knowledge the best currently available evidence for guiding clinical decision-making,” the investigators said.

Taken together, the findings from the current and previous studies support that empagliflozin and dapagliflozin provide comparable cardiorenal protection in patients T2D, they added.