Comparison of SGLT2 Inhibitors for New-Onset Proteinuria Risk in Patients With Type 2 Diabetes and Preserved Kidney Function.

AIMS: To compare the effects of individual SGLT2 inhibitors on preventing new-onset proteinuria in patients with type 2 diabetes and preserved kidney function.

MATERIALS AND

METHODS

A target trial emulation was performed using commercially available databases, including health checkups and claims data, between April 1, 2014 and March 31, 2023. Patients with type 2 diabetes (HbA1c ≥ 6.5%, use of antidiabetic drugs, and/or disease codes of type 2 diabetes) and preserved kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2, urinary protein < 1+ and without past history of chronic kidney disease) were included. We compared the risk of new-onset proteinuria among new users of empagliflozin, dapagliflozin and canagliflozin using the inverse probability of treatment weighting to adjust for baseline confounders and the inverse probability of censoring weighting to account for loss to follow-up.

RESULTS

The mean age was 67.5 ± 10.3 years, and 60% were men. The mean HbA1c level and eGFR were 7.56% ± 1.32% and 75.0 ± 8.0 mL/min/1.73 m2, respectively. During the median follow-up of 522 [263-925] days, new-onset proteinuria occurred in 43, 66 and 48 empagliflozin, dapagliflozin and canagliflozin users, respectively. Dapagliflozin showed a higher risk of new-onset proteinuria (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.15-2.33) than empagliflozin, particularly in men (HR, 2.34; 95% CI, 1.53-3.58) (p for heterogeneity < 0.01).

CONCLUSIONS

Empagliflozin was associated with a lower risk of new-onset proteinuria compared with dapagliflozin. These findings underscore the importance of individualised SGLT2 inhibitor selection but require confirmation in randomised controlled trials.