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The albuminuria‐lowering response to dapagliflozin is variable and reproducible among individual patients
Author(s) -
Petrykiv Sergei I.,
Laverman Gozewijn D.,
de Zeeuw Dick,
Heerspink Hiddo J. L.
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12936
Subject(s) - dapagliflozin , albuminuria , medicine , placebo , urology , creatinine , renal function , excretion , type 2 diabetes , diabetes mellitus , endocrinology , alternative medicine , pathology
Aims 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. Material and methods 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 ( ACEi ) or angiotensin receptor blocker ( ARB ) 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 UAE ). To assess reproducibility in individual albuminuria response, responses from the first and second exposure to dapagliflozin were correlated. Results A total of 33 patients (age, 61 years; female gender, 24.2%; median 24 h UAE , 470 mg/24 h) completed the study. Dapagliflozin, as compared to placebo, reduced 24 h UAE by 36.2% (95% CI , 22.9‐47.2; P < .001). Systolic blood pressure fell by 5.2 mm Hg (95% CI , 0.5‐10.0) and eGFR by 5.3 (95% CI , 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 UAE 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% CI , 0.27‐0.89]; P < .004). Conclusion Dapagliflozin significantly reduces albuminuria when given as adjunct to ACEi or ARB . 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.