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Comparative Study
. 2025 Mar 1;185(3):314-323.
doi: 10.1001/jamainternmed.2024.7381.

Effectiveness of Empagliflozin vs Dapagliflozin for Kidney Outcomes in Type 2 Diabetes

Kasper Bonnesen  1   2 , Uffe Heide-Jørgensen  1   2 , Diana H Christensen  1   2   3 , Christian F Christiansen  1   2 , Timothy L Lash  4 , Sean Hennessy  5 , Anthony A Matthews  6 , Lars Pedersen  1   2 , Reimar W Thomsen  1   2 , Morten Schmidt  1   2   7
Affiliations
Comparative Study

Effectiveness of Empagliflozin vs Dapagliflozin for Kidney Outcomes in Type 2 Diabetes

Kasper Bonnesen et al. JAMA Intern Med. .

Abstract

Importance: No large randomized clinical trial has directly compared empagliflozin with dapagliflozin, leaving their comparative effectiveness regarding kidney outcomes unknown.

Objective: To compare kidney outcomes between initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who were receiving antihyperglycemic treatment.

Design, setting, and participants: This target trial emulation used nationwide, population-based routinely collected Danish health care data to compare initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who received antihyperglycemic treatment between June 1, 2014, and October 31, 2020. Data were analyzed from October 2023 to August 2024. Persons were followed up until an outcome, emigration, death, 6 years, or December 31, 2021, whichever occurred first.

Exposure: Initiation of empagliflozin vs dapagliflozin.

Main outcomes and measures: Outcomes included acute kidney injury, incident chronic kidney disease (stages G3 to G5 or stage A2 or A3), and progression of chronic kidney disease (≥40% decrease in estimated glomerular filtration rate from baseline). Risks of kidney outcomes were estimated in intention-to-treat and per-protocol analyses using an Aalen-Johansen estimator that adjusted for 56 potential confounders and considered death as a competing event.

Results: A total of 32 819 individuals who initiated treatment with empagliflozin and 17 464 with dapagliflozin were included (median [IQR] age, 63 [54-71] years; 18 872 female individuals [37.5%]; median [IQR] estimated glomerular filtration rate, 88 [73-104] mL/min/1.73 m2). After weighting, all measured covariates were well balanced between the groups. In intention-to-treat analyses, people who initiated treatment with empagliflozin and dapagliflozin exhibited comparable 6-year risks of acute kidney injury (18.2% vs 18.5%; risk ratio, 0.98; 95% CI, 0.91-1.06), chronic kidney disease stages G3 to G5 (11.8% vs 12.1%; risk ratio, 0.97; 95% CI, 0.89-1.05), chronic kidney disease stage A2 or A3 (14.8% vs 14.3%; risk ratio, 1.04; 95% CI, 0.93-1.15), and progression of chronic kidney disease (5.3% vs 5.7%; risk ratio, 0.94; 95% CI, 0.56-1.58). The primary analyses were supported by corresponding per-protocol analyses.

Conclusions and relevance: The results of this cohort study suggest that people with type 2 diabetes who initiated treatment with empagliflozin and dapagliflozin had comparable long-term kidney outcomes.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bonnesen reported grants from the Danish Diabetes and Endocrine Academy, Danish Cardiovascular Academy, Helge Peetz og Verner Peetz og Hustru Vilma Peetz Legat, Danish Data Science Academy, Christian og Ottilia Brorsons Rejselegat, and Karl G. Andersen Fond during the conduct of the study. Dr Heide-Jørgensen reported involvement in studies with funding from various companies as research grants to (and administered by) Aarhus University. Dr Christensen reported grants from the Danish Diabetes and Endocrine Society, Danish Diabetes and Endocrine Academy, and Novo Nordisk Foundation during the conduct of the study as well as Independent Research Fund Denmark outside the submitted work. Dr Lash reported that he is a member of the Amgen Epidemiology Methods Advisory Council, for which he receives consulting fees and travel support. Dr Hennessy reported personal fees from the Medullary Thyroid Carcinoma Registry Consortium (Novo Nordisk, AstraZeneca, and Eli Lilly) outside the submitted work. Dr Thomsen reported that the Department of Clinical Epidemiology of Aarhus University and Aarhus University Hospital receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. No other disclosures were reported.

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References

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