Trial reportJournal of the American Heart Association2021
Association Between Circulating GDF-15 and Cardio-Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial.
Trial report in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Association of growth differentiation factor-15 with renal disease outcomes and all-cause death in type 1 and type 2 diabetic patients: a meta-analysis.BMC nephrology · 2025Pooled it
- Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.The Cochrane database of systematic reviews · 2024Pooled it
- Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.Biomolecules · 2022Pooled it
- The Role of GDF-15 in Heart Failure and Biomarker Potential-From Basic Science to Clinical Praxis.Biology · 2026Review
- Systems biology approach uncovers candidates for kidney-heart interorgan crosstalk after myocardial infarction.Scientific reports · 2025Article
- Association of Difference Between eGFR From Cystatin C and Creatinine and Serum GDF-15 With Adverse Outcomes in Diabetes Mellitus.Journal of cachexia, sarcopenia and muscle · 2025Article
- 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
- Growth Differentiation Factor 15 is Correlated With Urinary Markers in Patients with Chronic Heart Failure.Arquivos brasileiros de cardiologia · 2025Article
- The value of growth differentiation factor 15 as a biomarker for peripheral artery disease in diabetes patients.Diabetology & metabolic syndrome · 2025Article
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- Role of GDF-15 in diabetic nephropathy: mechanisms, diagnosis, and therapeutic potential.International urology and nephrology · 2025Review
- Review
- Plasma proteomics of acute tubular injury.Nature communications · 2024Article
- Obesity and the kidney: mechanistic links and therapeutic advances.Nature reviews. Endocrinology · 2024Review
- Growth differentiation factor-15 in patients with or at risk of heart failure but before first hospitalisation.Heart (British Cardiac Society) · 2024Article
- Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review.Communications medicine · 2023Article
- Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.Journal of geriatric cardiology : JGC · 2023Article
- Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors.medRxiv : the preprint server for health sciences · 2023Article
- 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 Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Studies have suggested that sodium glucose co-transporter 2 inhibitors exert anti-inflammatory effects. We examined the association of baseline growth differentiation factor-15 (GDF-15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with type 2 diabetes in the CANVAS (Canagliflozin Cardiovascular Assessment Study) and determined the effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on circulating GDF-15. Methods and Results The CANVAS trial randomized 4330 people with type 2 diabetes at high cardiovascular risk to canagliflozin or placebo. The association between baseline GDF-15 and cardiovascular (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death), HF, and kidney (40% estimated glomerular filtration rate decline, end-stage kidney disease, renal death) outcomes was assessed using multivariable adjusted Cox regression models. During median follow-up of 6.1 years (N=3549 participants with available samples), 555 cardiovascular, 129 HF, and 137 kidney outcomes occurred. Each doubling in baseline GDF-15 was significantly associated with a higher risk of cardiovascular (hazard ratio [HR], 1.2; 95% CI, 1.0‒1.3), HF (HR, 1.5; 95% CI, 1.2‒2.0) and kidney (HR, 1.5; 95% CI, 1.2‒2.0) outcomes. Baseline GDF-15 did not modify canagliflozin's effect on cardiovascular, HF, and kidney outcomes. Canaglifozin treatment modestly lowered GDF-15 compared with placebo; however, GDF-15 did not mediate the protective effect of canagliflozin on cardiovascular, HF, or kidney outcomes. Conclusions In patients with type 2 diabetes at high cardiovascular risk, higher GDF-15 levels were associated with a higher risk of cardiovascular, HF, and kidney outcomes. Canagliflozin modestly lowered GDF-15, but GDF-15 reduction did not mediate the protective effect of canagliflozin.
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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 Socratic graph.