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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  • Additional Information
    • Source:
      Publisher: American Diabetes Association Country of Publication: United States NLM ID: 7805975 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1935-5548 (Electronic) Linking ISSN: 01495992 NLM ISO Abbreviation: Diabetes Care Subsets: MEDLINE
    • Publication Information:
      Publication: Alexandria Va : American Diabetes Association
      Original Publication: New York, American Diabetes Assn.
    • Subject Terms:
      Diabetes Mellitus, Type 2*/drug therapy ; Sodium, Dietary* ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use; Benzhydryl Compounds/therapeutic use ; Blood Glucose ; Glucosides ; Humans ; Kidney ; Natriuretic Agents
    • Abstract:
      Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the 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.
      Research Design and Methods: The DAPASALT trial was a mechanistic, nonrandomized, 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-h blood pressure, and extracellular, intracellular, and plasma volumes at the start of treatment (ST) (days 2-4), end of treatment (ET) (days 12-14), and follow-up (FU) (days 15-18).
      Results: Fourteen patients were included in the efficacy analysis. Mean (SD) baseline sodium excretion (150 [32] mmol/24-h) did not significantly change during treatment (change at ST: -7.0 mmol/24-h [95% CI -22.4, 8.4]; change at ET: 2.1 mmol/24-h [-28.8, 33.0]). Mean baseline 24-h systolic blood pressure was 128 (10) mmHg and significantly reduced at ST (-6.1 mmHg [-9.1, -3.1]; P < 0.001) and ET (-7.2 mmHg [-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 [-1.3, -0.1]; P = 0.02). As expected, 24-h 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.
      (© 2020 by the American Diabetes Association.)
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    • Molecular Sequence:
      ClinicalTrials.gov NCT03152084
      figshare 10.2337/figshare.13232276
    • Accession Number:
      0 (Benzhydryl Compounds)
      0 (Blood Glucose)
      0 (Glucosides)
      0 (Natriuretic Agents)
      0 (Sodium, Dietary)
      0 (Sodium-Glucose Transporter 2 Inhibitors)
      1ULL0QJ8UC (dapagliflozin)
    • Publication Date:
      Date Created: 20201215 Date Completed: 20210820 Latest Revision: 20220322
    • Publication Date:
      20221213
    • Accession Number:
      PMC7818331
    • Accession Number:
      10.2337/dc20-2604
    • Accession Number:
      33318125