Effects of the sodium‐glucose cotransporter 2 inhibitor dapagliflozin on fluid distribution: A comparison study with furosemide and tolvaptan
Abstract
Aim: Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic properties. We recently reported that an SGLT2 inhibitor ameliorated extracellular fluid expansion with a transient increase in urinary Na+ excretion. However, the effects of SGLT2 inhibitors on fluid distribution in comparison to conventional diuretics remain unclear. Methods: Forty chronic kidney disease patients with fluid retention (average estimated glomerular filtration rate 29.2 ± 3.2 mL/min per 1.73 m 2) were divided into the SGLT2 inhibitor dapagliflozin (DAPA), loop diuretic furosemide (FR) and vasopressin V2 receptor antagonist tolvaptan (TLV). The body fluid volume was measured on days 0 and 7 using a bioimpedance analysis device. Results: In all three groups, body weight was significantly and similarly decreased, and urine volume numerically increased for 7 days. Bioimpedance analysis showed that the changes in intracellular water were similar, but that there were significant changes in the extracellular water (ECW) (DAPA −8.4 ± 1.7, FR −12.5 ± 1.3, TLV −7.4 ± 1.5%, P = 0.048). As a result, the change in the ratio of ECW to total body water in the DAPA group was significantly smaller than that in the FR group, but numerically larger than that in the TLV group (DAPA −1.5 ± 0.5, FR −3.6 ± 0.5, TLV −0.5 ± 0.4%, P < 0.001). Conclusion: Sodium‐glucose cotransporter 2 inhibitor DAPA predominantly decreased the ECW with a mild increase in urine volume, but the change in the ECW/total body water was smaller than that in patients treated with FR, and larger than that in patients treated with TLV, suggesting that the effects of SGLT2 inhibitors on fluid distribution may differ from those of conventional diuretics.
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The magnitude of a hemodynamic or natriuretic action of empagliflozin appears to be modest and is typically short-lived.
“Although the early benefits of empagliflozin to prevent clinical deterioration may suggest the possibility of a hemodynamic or natriuretic effect, the magnitude of such an action appears to be modest and is typically short-lived.”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [29]
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- Authors
- Ohara, K., Masuda, T., Murakami, T., Imai, T., Yoshizawa, H., Nakagawa, S., Okada, M., Miki, A., Myoga, A., Sugase, T., Sekiguchi, C., Miyazawa, Y., Maeshima, A., Akimoto, T., Saito, O., Muto, S., & Nagata, D.
- Affiliations
- Jichi Medical University (JP)
- Department of Surgery Nasu Minami Hospital Tochigi Japan
- Department of Internal Medicine Nasu Minami Hospital Tochigi Japan
- Corresponding author
- Masuda, Takahiro
- ORCID
- Venue
- Nephrology
- Publisher
- Wiley
- Published
- 2019-05-02
- Volume
- 24
- Issue
- 9
- Pages
- 904-911
- ISSN
- 1320-5358 (ISSN-L)
- 1440-1797
- OpenAlex
- W2906340657
- Cited by
- 81
- References
- 29
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 10 · 2023: 14 · 2022: 9 · 2021: 15 · 2020: 17 · 2019: 4
- FWCI
- 7.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Grant-in-Aid for Research on Advanced Chronic Kidney Disease, Practical Research Project for Renal Diseases from the Japan Agency for Medical Research and Development
- Grant-in-Aid for Young Scientists (15K21321)
- Jichi Medical University Young Investigator Award
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- dapagliflozin, SGLT2 inhibitors, fluid distribution, extracellular water, fluid retention, chronic kidney disease, furosemide, tolvaptan, loop diuretics, vasopressin V2 receptor antagonist, diuretic effect, bioelectrical impedance analysis, urine output
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Tolvaptan, Aged, Benzhydryl Compounds, Body Composition, Female, Furosemide, Glucosides, Humans, Male, Prospective Studies, Time Factors, Water-Electrolyte Balance, Water-Electrolyte Imbalance, Treatment Outcome, Fluid Shifts, Sodium Potassium Chloride Symporter Inhibitors, Renal Insufficiency, Chronic, Antidiuretic Hormone Receptor Antagonists
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