The albuminuria‐lowering response to dapagliflozin is variable and reproducible among individual patients

<jats:sec> <jats:title>Aims</jats:title> <jats:p>Albuminuria reduction is essential for renal and cardiovascular protection. We characterized the efficacy of dapagliflozin, a sodium‐glucose co‐transporter 2 inhibitor, on albuminuria. Secondly, we assessed whether the albuminuria‐lowering effect varies among patients, and whether this variability in response is reproducible.</jats:p> </jats:sec> <jats:sec> <jats:title>Material and methods</jats:title> <jats:p> A double‐blind, randomized, placebo controlled crossover trial was conducted. Patients with type 2 diabetes and albumin:creatinine ratio > 100 mg/g on a stable dose of an angiotensin‐converting enzyme inhibitor ( <jats:styled-content style="fixed-case">ACEi</jats:styled-content> ) or angiotensin receptor blocker ( <jats:styled-content style="fixed-case">ARB</jats:styled-content> ) were enrolled. Patients were assigned to 6‐week treatment periods with dapagliflozin 10 mg/d or placebo in random order, separated by 6‐weeks wash‐out periods. After the 2 treatment periods, half of the patients were re‐exposed for 6 weeks to dapagliflozin 10 mg/d. Primary outcome was change in 24‐hour urinary albumin excretion rate (24 h <jats:styled-content style="fixed-case">UAE</jats:styled-content> ). To assess reproducibility in individual albuminuria response, responses from the first and second exposure to dapagliflozin were correlated. </jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> A total of 33 patients (age, 61 years; female gender, 24.2%; median 24 h <jats:styled-content style="fixed-case">UAE</jats:styled-content> , 470 mg/24 h) completed the study. Dapagliflozin, as compared to placebo, reduced 24 h <jats:styled-content style="fixed-case">UAE</jats:styled-content> by 36.2% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content> , 22.9‐47.2; <jats:italic> <jats:styled-content style="fixed-case">P</jats:styled-content> </jats:italic>  < .001). Systolic blood pressure fell by 5.2 <jats:styled-content style="fixed-case">mm Hg</jats:styled-content> (95% <jats:styled-content style="fixed-case">CI</jats:styled-content> , 0.5‐10.0) and <jats:styled-content style="fixed-case">eGFR</jats:styled-content> by 5.3 (95% <jats:styled-content style="fixed-case">CI</jats:styled-content> , 2.7‐8.0). All effects were reversible directly after treatment discontinuation. In a subgroup of 15 patients who were exposed twice to dapagliflozin, 24 h <jats:styled-content style="fixed-case">UAE</jats:styled-content> responses showed a large variation among individuals: first exposure (range, −76% to +52%) and second exposure (−90% to +95%) and first and second individual response were significantly correlated (r = 0.69 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> , 0.27‐0.89]; <jats:italic> <jats:styled-content style="fixed-case">P</jats:styled-content> </jats:italic>  < .004). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p> Dapagliflozin significantly reduces albuminuria when given as adjunct to <jats:styled-content style="fixed-case">ACEi</jats:styled-content> or <jats:styled-content style="fixed-case">ARB</jats:styled-content> . The albuminuria response to dapagliflozin markedly varies among patients. This variation is not a random phenomenon, but is reproducible upon re‐exposure. These data support personalized therapy approaches to optimize diabetic kidney disease. </jats:p> </jats:sec>