ReviewInternational journal of molecular sciences2021
The Hormetic Effect of Metformin: "Less Is More"?
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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
19 citing papers in PubMed, 25 citations in OpenAlex.
- Context-Dependent Modulation of Ferroptosis by Metformin: Mechanisms, Therapeutic Implications and Open Questions.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- Neuroprotective efficacy of berberine and caffeine against rotenone-induced neuroinflammatory and oxidative disturbances associated with Parkinson's disease via inhibiting α-synuclein aggregation and boosting dopamine release.Inflammopharmacology · 2025Article
- Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.International journal of molecular sciences · 2025Review
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Antidiabetic Effects and Mechanisms of Action of Uncaria gambir Roxb. in Diabetic Sprague-Dawley Rats.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025Article
- Effect of metformin on cell proliferation and apoptosis in steatosis HepG2 cell model.Northern clinics of Istanbul · 2025Article
- Ethnopharmacological Study ofPlants (Basel, Switzerland) · 2024Article
- Yiqihuoxue decoction (GSC) inhibits mitochondrial fission through the AMPK pathway to ameliorate EPCs senescence and optimize vascular aging transplantation regimens.Chinese medicine · 2024Article
- Duodenal-jejunal bypass surgery activates eNOS and enhances antioxidant system by activating AMPK pathway to improve heart oxidative stress in diabetic cardiomyopathy rats.Journal of diabetes · 2024Article
- Diabetes Pharmacotherapy and its effects on the Skeletal Muscle Energy Metabolism.Mini reviews in medicinal chemistry · 2024Review
- Inside the Mechanism of Action of Three Pyrazole Derivatives in Human Platelets and Endothelial Cells.Antioxidants (Basel, Switzerland) · 2023Article
- Metformin Acutely Mitigates Oxidative Stress in Human Atrial Tissue: A Pilot Study in Overweight Non-Diabetic Cardiac Patients.Life (Basel, Switzerland) · 2022Article
- Regulatory Effects of Metformin, an Antidiabetic Biguanide Drug, on the Metabolism of Primary Rat Adipocytes.Molecules (Basel, Switzerland) · 2022Article
- Metformin Intervention-A Panacea for Cancer Treatment?Cancers · 2022Review
- Low-Dose Metformin as a Monotherapy Does Not Reduce Non-Small-Cell Lung Cancer Tumor Burden in Mice.Biomedicines · 2021Article
- Advances in research on pharmacotherapy of sarcopenia.Aging medicine (Milton (N.S.W)) · 2021Review
- A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan.Frontiers in endocrinology · 2021Review
- Sedentary Lifestyles and a Hypercaloric Diets During Middle Age, are Binomial Conducive to Fatal Progression, That is Counteracted by the Hormetic Treatment of Exercise, Metformin, and Tert-Butyl Hydroquinone: An Analysis of Female Middle-Aged Rat Liver Mitochondria.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin (MTF) is the first-line therapy for type 2 diabetes (T2DM). The euglycemic effect of MTF is due to the inhibition of hepatic glucose production. Literature reports that the principal molecular mechanism of MTF is the activation of 5'-AMP-activated protein kinase (AMPK) due to the decrement of ATP intracellular content consequent to the inhibition of Complex I, although this effect is obtained only at millimolar concentrations. Conversely, micromolar MTF seems to activate the mitochondrial electron transport chain, increasing ATP production and limiting oxidative stress. This evidence sustains the idea that MTF exerts a hormetic effect based on its concentration in the target tissue. Therefore, in this review we describe the effects of MTF on T2DM on the principal target organs, such as liver, gut, adipose tissue, endothelium, heart, and skeletal muscle. In particular, data indicate that all organs, except the gut, accumulate MTF in the micromolar range when administered in therapeutic doses, unmasking molecular mechanisms that do not depend on Complex I inhibition.
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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.