Effect of the sodium glucose co‐transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus
Abstract
Aim: To evaluate the effects of canagliflozin on plasma volume, urinary glucose excretion ( UGE ), fasting plasma glucose ( FPG ), glycated haemoglobin ( HbA1c ) and additional measures of fluid/electrolyte balance in patients with type 2 diabetes on background therapy with metformin and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers. Methods: Patients ( N = 36) were randomized (1 : 1) to receive canagliflozin 300 mg or placebo for 12 weeks. Pharmacodynamic parameters were assessed at baseline and at weeks 1 and 12. Results: Increased 24‐h UGE was seen in the canagliflozin group compared with a reduction in the placebo group at both week 1 (91.8 vs. −2.4 g) and week 12 (82.6 vs. −0.4 g). Canagliflozin also reduced both FPG and HbA1c . Reductions in body weight and blood pressure were observed at weeks 1 and 12. Canagliflozin decreased plasma volume compared with an increase with placebo at week 1 (−5.4 vs. 4.3%; p = 0.02), but this was largely attenuated at week 12 (4.6 vs. 5.8%; p = 0.76). A modest numerical increase in urine volume was observed with canagliflozin at week 1 that was attenuated at week 12; other measures of volume status (i.e. blood urea nitrogen, serum creatinine and haematocrit) remained modestly increased with canagliflozin at week 12. Conclusion: Canagliflozin provided sustained effects on UGE and FPG over 12 weeks and a transient reduction in plasma volume that was largely attenuated by week 12.
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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 [28]
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- Authors
- Sha, S., Polidori, D., Heise, T., Natarajan, J., Farrell, K., Wang, S. ‐., Sica, D., Rothenberg, P., & Plum‐Mörschel, L.
- Affiliations
- Janssen Research & Development (United States) (US)
- Janssen Research & Development, LLC San Diego CA USA
- Profil Institute for Metabolic Research (DE)
- Virginia Commonwealth University Medical Center (US)
- Corresponding author
- Sha, S.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2014-07-08
- Volume
- 16
- Issue
- 11
- Pages
- 1087-1095
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2024878386
- Cited by
- 249
- References
- 31
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 15 · 2023: 16 · 2022: 27 · 2021: 30 · 2020: 38 · 2019: 25 · 2018: 19 · 2017: 20 · 2016: 18 · 2015: 18 · 2014: 8
- FWCI
- 17.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Janssen Global Services, LLC
- 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
- canagliflozin, SGLT2 inhibitors, plasma volume, type 2 diabetes, urinary glucose excretion, fasting blood glucose, HbA1c, fluid and electrolyte balance, metformin, ACE inhibitors, angiotensin receptor blockers, blood pressure, body weight
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Adult, Aged, Antihypertensive Agents, Blood Glucose, Blood Pressure, Body Weight, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Dose-Response Relationship, Drug, Drug Therapy, Combination, Fasting, Female, Glucosides, Glycated Hemoglobin, Humans, Hypertension, Hypoglycemic Agents, Kidney, Male, Metformin, Middle Aged, Plasma Volume, Thiophenes, Water-Electrolyte Balance, Weight Loss, Treatment Outcome
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