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Natriuretic Effect of Two Weeks of Dapagliflozin Treatment in Patients With Type 2 Diabetes and Preserved Kidney Function During Standardized Sodium Intake: Results of the DAPASALT Trial

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posted on 14.12.2020, 17:20 by Rosalie A. Scholtes, Marcel H.A. Muskiet, Michiel .J.B. van Baar, Anne C. Hesp, Peter J. Greasley, Cecilia Karlsson, Ann Hammarstedt, Niki Arya, Daniël H. van Raalte, Hiddo J.L. Heerspink
Background:

Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce risk for heart failure hospitalization, potentially by inducing sodium excretion, osmotic diuresis and plasma volume contraction. Few studies have investigated this hypothesis, but none have assessed cumulative sodium excretion with SGLT2 inhibition during standardized sodium intake in patients with type 2 diabetes.

Methods:

DAPASALT (NCT03152084) was a mechanistic, non-randomized, open-label study in patients with type 2 diabetes with preserved kidney function, on a controlled standardized sodium diet (150 mmol/day). It evaluated the effects of dapagliflozin on sodium excretion, 24-hour blood pressure, and extracellular, intracellular and plasma volumes at start of treatment (ST; days 2-4), end of treatment (ET; days_12-14) and at follow-up (FU; days_15-18).

Results:

Fourteen patients were included in the efficacy analysis. Mean [SD] baseline sodium excretion (150 [32] mmol/24-hours), did not significantly change during treatment (change at ST: -7.0 mmol/24-hours [95%CI: -22.4, 8.4]; change at ET 2.1 mmol/24-hours [95%CI: -28.8, 33.0]). Mean (SD) baseline 24-hour systolic blood pressure was 128 (10) mmHg and significantly reduced at ST (-6.1 mmHg [95%CI: -9.1, -3.1]; p<0.001) and ET (-7.2 mmHg [95%CI: -10.0, -4.3]; p<0.001). Dapagliflozin did not significantly alter plasma volume or intracellular volume, while extracellular volume changed at ST (-0.7 L [95%CI: -1.3, 0.1]; p=0.02). As expected, 24-hour urinary glucose excretion significantly increased during dapagliflozin treatment and reversed during FU.

Conclusions:

During standardized sodium intake, dapagliflozin reduced blood pressure without clear changes in urinary sodium excretion, suggesting that factors other than natriuresis and volume changes may contribute to the blood-pressure lowering effects.

Funding

This study was funded by AstraZeneca.

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