Effects of the sodium-glucose co-transporter-2 inhibitor dapagliflozin on estimated plasma volume in patients with type 2 diabetes
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Aims: To compare the effects of the sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor dapagliflozin on estimated (ePV) and measured plasma volume (mPV) and to characterize the effects of dapagliflozin on ePV in a broad population of patients with type 2 diabetes. Materials and methods: The Strauss formula was used to calculate changes in ePV. Change in plasma volume measured with 125 I‐human serum albumin (mPV) was compared with change in ePV in 10 patients with type 2 diabetes randomized to dapagliflozin 10 mg/d or placebo. Subsequently, changes in ePV were measured in a pooled database of 13 phase 2b/3 placebo‐controlled clinical trials involving 4533 patients with type 2 diabetes who were randomized to dapagliflozin 10 mg daily or matched placebo. Results: The median change in ePV was similar to the median change in mPV (−9.4% and −9.0%) during dapagliflozin treatment. In the pooled analysis of clinical trials, dapagliflozin decreased ePV by 9.6% (95% confidence interval 9.0 to 10.2) compared to placebo after 24 weeks. This effect was consistent in various patient subgroups, including subgroups with or without diuretic use or established cardiovascular disease. Conclusions: ePV may be used as a proxy to assess changes in plasma volume during dapagliflozin treatment. Dapagliflozin consistently decreased ePV compared to placebo in a broad population of patients with type 2 diabetes.
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SGLT2 inhibitors reduce NFkB, IL-6, MCP-1, and other inflammatory factors implicated in DKD in experimental diabetes models.
“SGLT2 inhibitors reduce nuclear factork B, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP1), and other inflammatory factors implicated in DKD pathogenesis in experimental models of diabetes (Dekkers et al., 2019; Mancini et al., 2018).”
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A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors
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- Authors
- Dekkers, C. C. J., Sjöström, C. D., Greasley, P. J., Cain, V., Boulton, D. W., & Heerspink, H. J. L.
- Affiliations
- University Medical Center Groningen (NL)
- AstraZeneca (Sweden) (SE)
- Bogier Clinical and IT Solutions Raleigh North Carolina
- AstraZeneca (United States) (US)
- Corresponding author
- Heerspink, Hiddo J. L.
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2019-09-17
- Volume
- 21
- Issue
- 12
- Pages
- 2667-2673
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC6899523
- OpenAlex
- W2967001872
- Cited by
- 106
- References
- 32
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 17 · 2023: 19 · 2022: 13 · 2021: 27 · 2020: 18 · 2019: 3
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- dapagliflozin, SGLT2 inhibitors, plasma volume, type 2 diabetes, diuretics, cardiovascular disease
- MeSH terms
- Serum Albumin, Human, Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Female, Glucosides, Heart Failure, Humans, Male, Middle Aged, Plasma Volume
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