ArticleTranslational research : the journal of laboratory and clinical medicine2021
Biphasic effect of metformin on human cardiac energetics.
Article in Translational research : the journal of laboratory and clinical medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials.BMC medicine · 2022Pooled it
- Dose-dependent effects of Metformin on proliferation and odontogenic differentiation of dental pulp stem cells.BMC oral health · 2026Article
- 3D Bioprinted Fat-Myocardium Model Unravels the Role of Adipocyte Hypertrophy in Atrial Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- Immune Checkpoint Restoration as a Therapeutic Strategy to Halt Diabetes-Driven Atherosclerosis.Biology · 2025Review
- Mitochondrial fusion and cristae reorganization facilitate acquisition of cardiomyocyte identity during reprogramming of murine fibroblasts.Cell reports · 2025Article
- Insulin resistance-induced mitochondrial dysfunction and pyroptosis in trophoblasts: protective role of metformin.BMC pregnancy and childbirth · 2025Article
- Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.International journal of molecular sciences · 2025Review
- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- Can we stop one heart from breaking: triumphs and challenges in cardiac reprogramming.Current opinion in genetics & development · 2023Review
- Acute, High Dose Metformin Therapy at Reperfusion Decreases Infarct Size in the High-Risk Aging Heart.Aging and disease · 2023Article
- Effects of Metformin on Ischemia/Reperfusion Injury: New Evidence and Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Metformin preconditioning protects against myocardial stunning and preserves protein translation in a mouse model of cardiac arrest.Journal of molecular and cellular cardiology plus · 2023Article
- Effect of metformin on intact mitochondria from liver and brain: Concept revisited.European journal of pharmacology · 2022Article
- Traditional Chinese Medicine Fufang-Zhenzhu-Tiaozhi capsule prevents renal injury in diabetic minipigs with coronary heart disease.Chinese medicine · 2022Article
- Prescription drugs and mitochondrial metabolism.Bioscience reports · 2022Review
- Effect of Metformin on T2D-Induced MAM CaInternational journal of molecular sciences · 2022Article
- Bioequivalence and Safety Assessment of Two Formulations of Metformin Hydrochloride Sustained-Release Tablets (YuantangDrugs in R&D · 2022Article
- Therapeutic vs. Suprapharmacological Metformin Concentrations: Different Effects on Energy Metabolism and Mitochondrial Function in Skeletal Muscle CellsFrontiers in pharmacology · 2022Article
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14 authors at 3 institutions in 1 country.
Funding
Abstract
Metformin is the first-line medication for treatment of type 2 diabetes and has been shown to reduce heart damage and death. However, mechanisms by which metformin protects human heart remain debated. The aim of the study was to evaluate the cardioprotective effect of metformin on cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) and mitochondria isolated from human cardiac tissue. At concentrations ≤2.5 mM, metformin significantly increased oxygen consumption rate (OCR) in the hiPSC-CMs by activating adenosine monophosphate activated protein kinase (AMPK)-dependent signaling and enhancing mitochondrial biogenesis. This effect was abrogated by compound C, an inhibitor of AMPK. At concentrations >5 mM, metformin inhibited the cellular OCR and triggered metabolic reprogramming by enhancing glycolysis and glutaminolysis in the cardiomyocytes. In isolated cardiac mitochondria, metformin did not increase the OCR at any concentrations but inhibited the OCR starting at 1 mM through direct inhibition of electron-transport chain complex I. This was associated with reduction of superoxide production and attenuation of Ca
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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.