Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan

Introduction

Sodium–glucose cotransporter 2 inhibitors such as dapagliflozin have been proven effective for slowing chronic kidney disease (CKD) progression in large outcomes trials that mainly included patients with higher levels of albuminuria. Understanding the real-world utilization and effectiveness of these drugs among patients with CKD with lower levels of albuminuria can inform clinical decision-making in this population.

Methods

Claims data from the USA and Japan were used to describe patients with CKD and urinary albumin-to-creatinine ratio (UACR) < 200 mg/g who were eligible for dapagliflozin 10 mg treatment (initiators and untreated) following its approval for CKD. A quantile regression analysis was performed to evaluate the effect of dapagliflozin 10 mg initiation versus no initiation on estimated glomerular filtration rate (eGFR) slope in a propensity score-matched cohort, using a prevalent new-user design.

Results

Dapagliflozin initiators (n = 20,407) mostly had stage 3–4 CKD (69–81% across databases). The most common comorbidities were type 2 diabetes, hypertension and cardiovascular disease. At baseline, a renin–angiotensin system inhibitor was prescribed in 53–81% of patients. Eligible but untreated patients were older and had a higher eGFR and lower comorbidity burden than initiators. Following dapagliflozin initiation, the differences in median eGFR slope between initiators and matched non-initiators were 1.07 mL/min/1.73 m²/year (95% confidence interval [CI] 0.40–1.74) in all patients with UACR < 200 mg/g and 1.28 mL/min/1.73 m²/year (95% CI − 1.56 to 4.12) in patients with UACR < 200 mg/g without type 2 diabetes.

Conclusions

Dapagliflozin 10 mg was prescribed to a broad range of patients with CKD. In patients with UACR < 200 mg/g, dapagliflozin initiation was associated with a clinically meaningful attenuation of eGFR slope compared with non-initiation. These findings supplement available clinical efficacy evidence and suggest that dapagliflozin effectiveness may extend to patients with CKD and UACR < 200 mg/g. Graphical Abstract and Video Abstract available for this article.

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Graphical Abstract