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June 28, 2021Cardiovascular DiabetologyOpen Access

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

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Key result

Empagliflozin significantly reduced estimated plasma volume by 5.60% and estimated extracellular volume by 144.4 mL compared to placebo at 24 weeks in patients with type 2 diabetes and cardiovascular disease.

Why the study?

SGLT2 inhibitors promote diuresis and reduce excess fluid volume to improve cardiovascular outcomes, but the specific effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and CVD required evaluation.

Does empagliflozin reduce estimated fluid volumes in adults with type 2 diabetes and established cardiovascular disease?

Comparison

Empagliflozin (10 mg once daily) vs placebo

Design

Post-hoc analysis of a multicenter, placebo-controlled, double-blind randomized controlled trial

Follow-up

24 weeks

Authors

ATAtsushi TanakaMSMichio ShimabukuroHTHiroki Teragawa

Discussion

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Overview

Provides mechanistic support for empagliflozin's early CV benefits; extends SGLT2 inhibitor trial data on volume effects in T2D with CVD.

Study Design

Type

RCT (n=105)

Blinding

Double-blind

Randomization

randomized

Multicenter

Yes

Structured PICO

Does empagliflozin reduce estimated fluid volumes in adults with type 2 diabetes and established cardiovascular disease?

P
Population
105 adults with type 2 diabetes and established cardiovascular disease were randomized to empagliflozin or placebo and followed for 24 weeks to assess changes in estimated fluid volumes.
I
Intervention
Empagliflozin 10 mg oral once daily for 24 weeks
C
Comparator
Matching placebo for 24 weeks
O
Outcome
Between-group differences in the percentage change in estimated plasma volume (ePV) and the change in estimated extracellular volume (eEV) from baseline to weeks 4, 12, and 24surrogate

Main Result

Mean Difference: -5.6 (95% CI -9.87–-1.32)

Absolute Event Rate: -6.66% vs -1.13%

Empagliflozin significantly reduces estimated plasma and extracellular volumes in patients with type 2 diabetes and cardiovascular disease, providing mechanistic insight into its early cardiovascular benefits.

Limitations

  • Post-hoc analysis
  • Small sample size
  • Estimations of fluid volumes limited to 4, 12, and 24 weeks
  • No direct measures of fluid volume were made

Cite This Study

Tanaka et al. (2021) conducted an RCT in Type 2 diabetes and cardiovascular disease (n=105). Empagliflozin vs. Placebo was evaluated on Percentage change in estimated plasma volume (ePV) from baseline to week 24 (MD -5.60%, 95% CI -9.87 to -1.32). Empagliflozin significantly reduced estimated plasma volume by 5.60% and estimated extracellular volume by 144.4 mL compared to placebo at 24 weeks in patients with type 2 diabetes and cardiovascular disease.

synapsesocial.com/papers/6a959afbd44cea3cdd82aff2https://doi.org/10.1186/s12933-021-01295-6
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Secondary analyses to assess the profound effects of empagliflozin on endothelial function in patients with type 2 diabetes and established cardiovascular diseases: The placebo‐controlled double‐blind randomized effect of empagliflozin on endothelial function in cardiovascular high risk diabetes mellitus: Multi‐center placebo‐controlled double‐blind randomized trial2020 · 26 citations
  2. 2Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial2017 · 32 citations
  3. 3Effects of Canagliflozin on Amino-Terminal Pro–B-Type Natriuretic Peptide2020 · 100 citations
  4. 4Possible Mechanism of Hematocrit Elevation by Sodium Glucose Cotransporter 2 Inhibitors and Associated Beneficial Renal and Cardiovascular Effects2019 · 279 citations
  5. 5Dapagliflozin a glucose‐regulating drug with diuretic properties in subjects with type 2 diabetes2013 · 838 citations