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Diabetes Obes Metab. 2017 Oct;19(10):1363-1370. doi: 10.1111/dom.12936. Epub 2017 Jun 8.

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

Author information

1
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
2
Department of Nephrology, Ziekenhuisgroep Twente, Almelo and Hengelo, the Netherlands.

Abstract

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.

KEYWORDS:

SGLT2 ; albuminuria; dapagliflozin; response variability; type 2 diabetes

PMID:
28295959
DOI:
10.1111/dom.12936
[Indexed for MEDLINE]

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