TY - JOUR
T1 - 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
AU - Scholtes, Rosalie A.
AU - Muskiet, Marcel H. A.
AU - van Baar, Michiel J. B.
AU - Hesp, Anne C.
AU - Greasley, Peter J.
AU - Karlsson, Cecilia
AU - Hammarstedt, Ann
AU - Arya, Niki
AU - van Raalte, Daniël H.
AU - Heerspink, Hiddo J. L.
N1 - Funding Information: Acknowledgments. The authors are extremely grateful to the participants who volunteered in the study. The authors acknowledge the help of dietician Esther Pekel for developing the food menus and the following study nurses and assistants who were indispensable in the process of data collection: Jeannette Boerop, Ingrid Knufman, and Renée de Meijer (Diabetes Center, Department of Internal Medicine, AUMC, location VUMC). The authors also thank the study team members at AstraZeneca. Finally, the authors thank Parita Sheth (inScience Communications, London, U.K.) for assistance with figure preparation and editing; this support was funded by AstraZeneca. Funding and Duality of Interest. The DAPA-SALT study was funded by AstraZeneca. M.H.A.M. hasactedasaspeaker/consultantforAstraZeneca, Eli Lilly, Novo Nordisk, and Sanofi; all honoraria are paid to his employer (AUMC, location VUMC). P.J.G., C.K., A.H., and N.A. are employees and shareholders at AstraZeneca. D.H.v.R. has acted as a consultant and received honoraria from Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi, and AstraZeneca and has received research operating funds from Boehringer Ingelheim-Lilly Diabetes Alliance, AstraZeneca, and Novo Nordisk; all honoraria are paid to his employer (AUMC, location VUMC). H.J.L.H. is consultant for AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Gilead Sciences, Janssen, Merck, Mundipharma, Mitsu-bishi Tanabe, Novo Nordisk, and Retrophin. He received research support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen. No other potential conflicts of interest relevant to this article were reported. Author Contributions. R.A.S., M.H.A.M., M.J.B.v.B., A.H., D.H.v.R., and H.J.L.H. were involved in data collection. R.A.S., D.H.v.R., and H.J.L.H. wrote the drafts of the manuscript. P.J.G., C.K., D.H.v.R., and H.J.L.H. designed the study. All authors were involved in the data analysis and interpretation and participated in critical review of the manuscript drafts and approved the final version for submission. R.A.S., D.H.v.R., and H.J.L. H. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented at the European Society of Cardiology Congress, 2020–The Digital Experience, 29 August–1 September, 2020. Publisher Copyright: © 2020 by the American Diabetes Association. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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: 27.0 mmol/24-h [95% CI 222.4, 8.4]; change at ET: 2.1 mmol/24-h [228.8, 33.0]). Mean baseline 24-h systolic blood pressure was 128 (10) mmHg and significantly reduced at ST (26.1 mmHg [29.1, 23.1]; P<0.001) and ET (27.2 mmHg [210.0, 24.3]; P<0.001). Dapagliflozin did not significantly alter plasma volume or intracellular volume, while extracellular volume changed at ST (20.7 L [21.3, 20.1]; P50.02).Asexpected,24-hurinaryglucoseexcretionsignificantlyincreasedduring 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.
AB - 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: 27.0 mmol/24-h [95% CI 222.4, 8.4]; change at ET: 2.1 mmol/24-h [228.8, 33.0]). Mean baseline 24-h systolic blood pressure was 128 (10) mmHg and significantly reduced at ST (26.1 mmHg [29.1, 23.1]; P<0.001) and ET (27.2 mmHg [210.0, 24.3]; P<0.001). Dapagliflozin did not significantly alter plasma volume or intracellular volume, while extracellular volume changed at ST (20.7 L [21.3, 20.1]; P50.02).Asexpected,24-hurinaryglucoseexcretionsignificantlyincreasedduring 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85099916577&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33318125
UR - http://www.scopus.com/inward/record.url?scp=85099916577&partnerID=8YFLogxK
U2 - https://doi.org/10.2337/dc20-2604
DO - https://doi.org/10.2337/dc20-2604
M3 - Article
C2 - 33318125
SN - 0149-5992
VL - 44
SP - 440
EP - 447
JO - Diabetes Care
JF - Diabetes Care
IS - 2
ER -