ArticleCirculation2022
Metabolomic Profiling of the Effects of Dapagliflozin in Heart Failure With Reduced Ejection Fraction: DEFINE-HF.
Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It reports registered trial NCT02653482. Cited by 57 papers, 3 of them syntheses that pooled it.
What it found
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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.
Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure
Diagnostic Utility of SGLT1/2 Inhibition to Facilitate Myocardial Glucose Suppression During Evaluation of Cardiac Inflammation on FDG-PET
Sodium-glucose Transporter Type 2 Inhibition in Anthracycline-related Cardiotoxicity - SPRINT
Who cites it
57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Effect of Hypoglycemic Drugs on Patients with Heart Failure with or without T2DM: A Bayesian Network Meta-analysis.Reviews in cardiovascular medicine · 2025Pooled it
- Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis.Cardiovascular diabetology · 2024Pooled it
- Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes.JCI insight · 2023Pooled it
- Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction.JACC. Heart failure · 2025Trial
- Statins Do Not Significantly Affect Oxidative Nitrosative Stress Biomarkers in the PREVENT Randomized Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Targeted Metabolomic Profiling of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The PRESERVED-HF Trial.JACC. Heart failure · 2024Trial
- Empagliflozin improves insulin sensitivity in patients with recent acute coronary syndrome and newly detected dysglycaemia : Experiences from the randomized, controlled SOCOGAMI trial.Cardiovascular diabetology · 2023Trial
- Trial
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Treatment with dapagliflozin and empagliflozin reduces concentrations of N4-acetylcytidine in plasma, a biomarker associated with vascular damage.Cardiovascular diabetology · 2026Article
- The Use of Metabolomes in Risk Stratification of Patients with Heart Failure: A Scoping Review.Life (Basel, Switzerland) · 2026Review
- Integrating ketone bodies in multi-marker risk prediction of incident heart failure in the multi-ethnic study of atherosclerosis.European journal of preventive cardiology · 2026Article
- Metabolic reprogramming in diabetes and other endocrine and metabolic disorders: exploring the Warburg effect, ketones, and SGLT2 inhibitors.Reviews in endocrine & metabolic disorders · 2026Review
- Mortality prediction in the elderly patients with coronary artery disease and atrial fibrillation: a retrospective machine learning approach.Frontiers in medicine · 2026Article
- Metabolic remodeling and cardiac functional adaptation mediated by dapagliflozin in patients with acute heart failure: a retrospective cohort study.Frontiers in pharmacology · 2026Article
- Heart failure with preserved ejection fraction in cancer patients and survivors. A scientific statement of the Heart Failure Association of the ESC and the ESC Council of Cardio-Oncology.European journal of heart failure · 2025Article
- Deletion of cardiac fibroblast growth factor-23 beneficially impacts myocardial energy metabolism in left ventricular hypertrophy.npj metabolic health and disease · 2025Article
- Review
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
20 authors at 12 institutions in 2 countries.
Funding
Abstract
backgroundSodium-glucose cotransporter-2 inhibitors are foundational therapy in patients with heart failure with reduced ejection fraction (HFrEF), but underlying mechanisms of benefit are not well defined. We sought to investigate the relationships between sodium-glucose cotransporter-2 inhibitor treatment, changes in metabolic pathways, and outcomes using targeted metabolomics.
methodsDEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients With HF With Reduced Ejection Fraction) was a placebo-controlled trial of dapagliflozin in HFrEF. We performed targeted mass spectrometry profiling of 63 metabolites (45 acylcarnitines [markers of fatty acid oxidation], 15 amino acids, and 3 conventional metabolites) in plasma samples at randomization and 12 weeks. Using mixed models, we identified principal components analysis-defined metabolite clusters that changed differentially with treatment and examined the relationship between change in metabolite clusters and change in Kansas City Cardiomyopathy Questionnaire scores and NT-proBNP (N-terminal probrain natriuretic peptide). Models were adjusted for relevant clinical covariates and nominal
resultsAmong the 234 DEFINE-HF participants with targeted metabolomic data, the mean age was 62.0±11.1 years, 25% were women, 38% were Black, and mean ejection fraction was 27±8%. Dapagliflozin increased ketone-related and short-chain acylcarnitine as well as medium-chain acylcarnitine principal components analysis-defined metabolite clusters compared with placebo (nominal
conclusionsIn this study of targeted metabolomics in a placebo-controlled trial of sodium-glucose cotransporter-2 inhibitors in HFrEF, we observed effects of dapagliflozin on key metabolic pathways, supporting a role for altered ketone and fatty acid biology with sodium-glucose cotransporter-2 inhibitors in patients with HFrEF. Only physiologic levels of ketosis were observed. In addition, we identified several metabolic biomarkers associated with adverse HFrEF outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02653482.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.