ArticleDiabetes2012
Metformin prevents the development of chronic heart failure in the SHHF rat model.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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.
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Who cites it
52 citing papers in PubMed, 127 citations in OpenAlex.
- Trial
- Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status.Circulation research · 2016Trial
- Trial
- Metformin inhibits proliferation of residing fibroadipogenic progenitor cells from failing human hearts.ESC heart failure · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and heart failure with preserved ejection fraction: A state-of-the-art review.World journal of cardiology · 2026Review
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- An Overview of Sex-Based Differences in the Onset and Progression of DKD in the Well-Known Model, ZSF1 Rats.Life (Basel, Switzerland) · 2025Article
- Temporal trends in incidence, clinical characteristics and outcomes among young adults with heart failure: a territory-wide study from 2014 to 2023 on 19,537 patients.The Lancet regional health. Western Pacific · 2025Article
- Cardiometabolic Dysregulation and Heart Failure.Reviews in cardiovascular medicine · 2025Review
- Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis.Journal of diabetes and metabolic disorders · 2024Review
- Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.Drug design, development and therapy · 2023Review
- The role of metabolic syndrome in sudden cardiac death risk: Recent evidence and future directions.European journal of clinical investigation · 2022Review
- Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence.Biomolecules · 2021Review
- AMPK protects against alcohol-induced liver injury through UQCRC2 to up-regulate mitophagy.Autophagy · 2021Article
- Normalizing glucose levels reconfigures the mammary tumor immune and metabolic microenvironment and decreases metastatic seeding.Cancer letters · 2021Article
- Fibrosis of the diabetic heart: Clinical significance, molecular mechanisms, and therapeutic opportunities.Advanced drug delivery reviews · 2021Review
- Metformin Reduces Vascular Assembly in High Glucose-Treated Human Microvascular Endothelial Cells in An AMPK-Independent Manner.Cell journal · 2021Article
- The Hormetic Effect of Metformin: "Less Is More"?International journal of molecular sciences · 2021Review
- Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications.Journal of clinical medicine · 2021Review
- Differential epigenetic factors in the prediction of cardiovascular risk in diabetic patients.European heart journal. Cardiovascular pharmacotherapy · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investigated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomized into three treatment groups as follows: 1) metformin (100 mg/kg per day), 2) rosiglitazone (2 mg/kg per day), and 3) no drug. Ten Sprague-Dawley rats served as normal controls. At the end of the treatment period (12 months), the cardiac phenotype was characterized by histology, echocardiography, and isolated perfused heart studies. Metformin attenuated left ventricular (LV) remodeling, as shown by reduced LV volumes, wall stress, perivascular fibrosis, and cardiac lipid accumulation. Metformin improved both systolic and diastolic indices as well as myocardial mechanical efficiency, as shown by improved ability to convert metabolic energy into mechanical work. Metformin induced a marked activation of AMP-activated protein kinase, endothelial nitric oxide synthase, and vascular endothelial growth factor and reduced tumor necrosis factor-α expression and myocyte apoptosis. Rosiglitazone did not affect LV remodeling, increased perivascular fibrosis, and promoted further cardiac lipid accumulation. In conclusion, long-term treatment with metformin, but not with rosiglitazone, prevents the development of severe CHF in the SHHF model by a wide-spectrum interaction that involves molecular, structural, functional, and metabolic-energetic mechanisms.
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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.