Trial reportCardiovascular diabetology2022
The effect of empagliflozin on growth differentiation factor 15 in patients with heart failure: a randomized controlled trial (Empire HF Biomarker).
Trial report in Cardiovascular diabetology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03198585. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Empagliflozin in Heart Failure Patients With Reduced Ejection Fraction: A Randomized Clinical Trial (Empire HF)
Open the trial in the graphWho cites it
17 citing papers in PubMed, 60 citations in OpenAlex.
- Review
- Growth differentiation factor-15 improves long-term mortality risk prediction beyond the GRACE 2.0 score after acute coronary syndrome.Scientific reports · 2026Article
- Evolving Insights Regarding Biomarkers to Better Manage Older Adults With Cardiovascular Disease.The journal of applied laboratory medicine · 2025Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway.Scientific reports · 2025Article
- Review
- Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Neurohumoral and Mitochondrial Activation in Patients With Diabetes.Journal of the American Heart Association · 2025Observational
- Observational
- Evaluating the Safety and Efficacy of SGLT-2 Inhibitors on Reducing Cardiovascular and Renal Mortality, Morbidity and Inflammatory Outcomes in Various Patient Populations: A Systematic Review and Meta-Analysis of 92 920 Patients.Clinical Medicine Insights. Cardiology · 2025Article
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- Representation of women and racial minorities in SGLT2 inhibitors and heart failure clinical trials.International journal of cardiology. Heart & vasculature · 2024Article
- Article
- The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors:JACC. CardioOncology · 2024Review
- Growth Differentiation Factor 15 (GDF-15), a New Biomarker in Heart Failure Management.Current heart failure reports · 2023Review
- Empagliflozin for Patients with Heart Failure and Type 2 Diabetes Mellitus: Clinical Evidence in Comparison with Other Sodium-Glucose Co-transporter-2 Inhibitors and Potential Mechanism.Journal of cardiovascular translational research · 2023Review
- The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest.Life (Basel, Switzerland) · 2022Review
- The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundPlasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients.
methodsThis Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed.
resultsA total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918-1720) pg/mL with empagliflozin, and 1299 (952-1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 [95% confidence interval (CI), 1.03-1.15]: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = - 0.23, p = 0.031), and end-diastolic volume (R = - 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 [95%CI, 0.86-1.38]: p = 0.48) or plasma hsTNT (1.07 [95%CI, 0.97-1.19]: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01.
conclusionEmpagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP.
trial registrationThe Empire HF trial is registered with ClinicalTrials.gov, NCT03198585.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.