A Danish nationwide cohort study using a target trial emulation framework examined kidney outcomes in individuals with type 2 diabetes who initiated treatment with either empagliflozin or dapagliflozin, two sodium-glucose cotransporter-2 inhibitors commonly used for managing hyperglycemia.
The study, published in JAMA Internal Medicine, found no significant differences between the two drugs in terms of acute kidney injury, chronic kidney disease (CKD) development, or progression over a follow-up period of up to six years.
The study included 32,819 individuals who started treatment with empagliflozin and 17,464 who initiated dapagliflozin between June 1, 2014, and October 31, 2020. The median age of participants was 63 years, with males comprising the majority (62.9% in the empagliflozin group and 61.7% in the dapagliflozin group). The median baseline estimated glomerular filtration rate was 88 mL/min/1.73 m2 (IQR, 73-104). The cohort was followed until an outcome event, emigration, death, six years, or December 31, 2021, whichever occurred first.
The 6-year risk of acute kidney injury was 18.2% for those on empagliflozin compared to 18.5% for those on dapagliflozin (risk ratio [RR], 0.98; 95% confidence interval [CI], 0.91-1.06).
Meanwhile, the risk of developing CKD stages G3 to G5 was 11.8% in the empagliflozin group and 12.1% in the dapagliflozin group (RR, 0.97; 95% CI, 0.89-1.05).
For CKD stage A2 or A3, the risk was 14.8% in the empagliflozin group and 14.3% in the dapagliflozin group (RR, 1.04; 95% CI, 0.93-1.15).
The progression of CKD was observed in 5.3% of those on empagliflozin and 5.7% of those on dapagliflozin (RR, 0.94; 95% CI, 0.56-1.58). These findings were consistent in both intention-to-treat and per-protocol analyses.
The study's findings support the current clinical practice of not preferentially recommending either empagliflozin or dapagliflozin based on kidney outcomes for individuals with type 2 diabetes. The study period was specifically chosen to be before SGLT2is obtained European approval for heart failure and CKD treatment in patients without type 2 diabetes.
A key limitation of the study was that treatment assignment was not randomized, leaving the potential for unmeasured or residual confounding. The researchers noted that in the absence of a large randomized clinical trial directly comparing these medications, this target trial emulation provides the best currently available evidence for clinical decision-making.
The study disclosed several conflicts of interest, with authors reporting research grants or personal fees from organizations such as the Novo Nordisk Foundation, Amgen, and other pharmaceutical companies. However, the study specifies that these funding sources had no role in the study's design, data analysis, manuscript preparation, or publication decisions.
