NDLI: Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

Content Provider	Springer Nature : BioMed Central
Author	Tanaka, Atsushi Shimabukuro, Michio Teragawa, Hiroki Okada, Yosuke Takamura, Toshinari Taguchi, Isao Toyoda, Shigeru Tomiyama, Hirofumi Ueda, Shinichiro Higashi, Yukihito Node, Koichi
Abstract	Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-021-01295-6.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-021-01295-6
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2021-06-28
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology Fluid volume Empagliflozin Heart failure Type 2 diabetes Cardiovascular disease N-terminal pro-brain natriuretic peptide
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

N-terminal Pro-B-Type Natriuretic Peptide, Left Ventricular Mass, and Incident Heart Failure

Plasma N-terminal pro-brain natriuretic peptide as a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria

Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial

Effect of empagliflozin on left ventricular contractility and peak oxygen uptake in subjects with type 2 diabetes without heart disease: results of the EMPA-HEART trial

Usefulness of amino terminal pro-B-type natriuretic peptide in evaluating children with cardiac failure.

Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

Serum N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated With Functional Capacity in Patients With Peripheral Arterial Disease

Long-term observation of estimated fluid volume reduction after the initiation of ipragliflozin in patients with type 2 diabetes mellitus: a sub-analysis from a randomized controlled trial (PROTECT)

The minimal informative monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure

Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

Similar Documents

N-terminal Pro-B-Type Natriuretic Peptide, Left Ventricular Mass, and Incident Heart Failure

Plasma N-terminal pro-brain natriuretic peptide as a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria

Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial

Effect of empagliflozin on left ventricular contractility and peak oxygen uptake in subjects with type 2 diabetes without heart disease: results of the EMPA-HEART trial

Usefulness of amino terminal pro-B-type natriuretic peptide in evaluating children with cardiac failure.

Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

Serum N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated With Functional Capacity in Patients With Peripheral Arterial Disease

Long-term observation of estimated fluid volume reduction after the initiation of ipragliflozin in patients with type 2 diabetes mellitus: a sub-analysis from a randomized controlled trial (PROTECT)

The minimal informative monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure

Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial