ArticlePloS one2014
Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 109 citations in OpenAlex.
- Optimizing the Interaction of Exercise Volume and Metformin to Induce a Clinically Significant Reduction in Metabolic Syndrome Severity: A Randomised Trial.International journal of environmental research and public health · 2020Trial
- Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.Aging cell · 2019Trial
- Divergent Retrograde Signaling Pathways Coordinate Longevity and Metformin Responses in Complex I and Complex IV DeficientbioRxiv : the preprint server for biology · 2026Article
- Drug safety in patients with mitochondrial disease: an observational cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Observational
- Metformin and insulin exacerbate one-carbon metabolism deficits in pregnant growth restricted rats and impacts the placenta, fetal liver and pancreas.The Journal of physiology · 2025Article
- Evaluation of the toxicity potential of exercise and atorvastatin/metformin combination therapy on STZ-diabetic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.International journal of molecular sciences · 2025Review
- Sex differences in the skeletal muscle response to metformin treatment and the possible association with gut-muscle axis in rats.Frontiers in endocrinology · 2025Article
- Platelet bioenergetics correlate with skeletal muscle respiration in a murine model of type II diabetes.Frontiers in molecular biosciences · 2025Article
- Effects of Hypoglycemic Agents on The Musculoskeletal System: A Comprehensive Review.Drug design, development and therapy · 2025Review
- Risk Factors for Sarcopenia in Women with Type 2 Diabetes and the Effects of Metformin: A Cross-Sectional Study of 7,731 Patients from the UK Biobank.International journal of women's health · 2025Article
- Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities.Aging cell · 2024Article
- Fungal Depsidones Stimulate AKT-Dependent Glucose Uptake in 3T3-L1 Adipocytes.Journal of natural products · 2024Article
- Role of Cardiorespiratory Fitness and Mitochondrial Oxidative Capacity in Reduced Walk Speed of Older Adults With Diabetes.Diabetes · 2024Article
- Combined Administration of Metformin and Vitamin D: A Futuristic Approach for Management of Hyperglycemia.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Redox state and altered pyruvate metabolism contribute to a dose-dependent metformin-induced lactate production of human myotubes.American journal of physiology. Cell physiology · 2023Article
- Article
- Understanding heterogeneity of responses to, and optimizing clinical efficacy of, exercise training in older adults: NIH NIA Workshop summary.GeroScience · 2023Review
- Antecedent Metabolic Health and Metformin (ANTHEM) Aging Study: Rationale and Study Design for a Randomized Controlled Trial.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Metformin Attenuates Slow-to-Fast Fiber Shift and Proteolysis Markers Increase in Rat Soleus after 7 Days of Rat Hindlimb Unloading.International journal of molecular sciences · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I of the mitochondrial respiratory chain. This seems contraindicative since muscle mitochondrial dysfunction has been linked to the pathogenesis of type 2 diabetes. However, its significance for in vivo skeletal muscle mitochondrial function has yet to be elucidated. The aim of this study was to assess the effects of metformin on in vivo and ex vivo skeletal muscle mitochondrial function in a rat model of diabetes. Healthy (fa/+) and diabetic (fa/fa) Zucker diabetic fatty rats were treated by oral gavage with metformin dissolved in water (30, 100 or 300 mg/kg bodyweight/day) or water as a control for 2 weeks. After 2 weeks of treatment, muscle oxidative capacity was assessed in vivo using 31P magnetic resonance spectroscopy and ex vivo by measuring oxygen consumption in isolated mitochondria using high-resolution respirometry. Two weeks of treatment with metformin impaired in vivo muscle oxidative capacity in a dose-dependent manner, both in healthy and diabetic rats. Whereas a dosage of 30 mg/kg/day had no significant effect, in vivo oxidative capacity was 21% and 48% lower after metformin treatment at 100 and 300 mg/kg/day, respectively, independent of genotype. High-resolution respirometry measurements demonstrated a similar dose-dependent effect of metformin on ex vivo mitochondrial function. In conclusion, metformin compromises in vivo and ex vivo muscle oxidative capacity in Zucker diabetic fatty rats in a dose-dependent manner.
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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.