ArticleCell metabolism2017
Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 6 of them syntheses that pooled it.
What it found
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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
237 citing papers in PubMed, 6 syntheses or guidelines pooled it, 395 citations in OpenAlex.
- Association Between Metformin Use and Risk of Lung Cancer in Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.Cancer reports (Hoboken, N.J.) · 2026 · on this mapPooled it
- Short-term neonatal outcomes in women with gestational diabetes treated using metformin versus insulin: a systematic review and meta-analysis of randomized controlled trials.Acta diabetologica · 2023Pooled it
- Pooled it
- Pooled it
- The addition of metformin to systemic anticancer therapy in advanced or metastatic cancers: a meta-analysis of randomized controlled trials.International journal of medical sciences · 2020Pooled it
- Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis.PLoS medicine · 2019Pooled it
- Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Trial
- Brain insulin resistance as a driver of proteinopathy in neurodegeneration: from cell-type-specific mechanisms to targeted therapeutics.Translational neurodegeneration · 2026Review
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Association of metformin with osteoarthritis progression and total joint arthroplasty: evidence from the UK Biobank, a large population-based cohort study.Clinical rheumatology · 2026Article
- Article
- Hyperactive muscle mTORC1 attenuates functional adaptations to endurance training despite alterations in mitochondrial and lipid profiles.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Article
- Evaluating the Impact of Putative Metformin Targets on Cancer Outcomes: A Drug-Target Mendelian Randomization Study.Diabetes, obesity & metabolism · 2026Article
- Metformin beyond Glycemic Control: New Mechanistic Insights and Expanding Therapeutic Horizons.Diabetes & metabolism journal · 2026Review
- Metformin for Longevity and Sarcopenia: A Therapeutic Paradox in Aging.Biomedicines · 2026Article
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- AMPK/mTORC2/AKT-473/RUNX2 signaling axis modulates epithelial-mesenchymal transition and bone tropism in breast cancer.Frontiers in oncology · 2026Article
- Controversial effects of metformin on human physiology and pathophysiology.Frontiers in pharmacology · 2026Review
- Metformin sensitizes non-small cell lung cancer to CDK4/6 inhibitor treatment by reducing lysosomal trapping.Science China. Life sciences · 2026Article
177 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Metformin is the most widely prescribed drug for the treatment of type 2 diabetes. However, knowledge of the full effects of metformin on biochemical pathways and processes in its primary target tissue, the liver, is limited. One established effect of metformin is to decrease cellular energy levels. The AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are key regulators of metabolism that are respectively activated and inhibited in acute response to cellular energy depletion. Here we show that metformin robustly inhibits mTORC1 in mouse liver tissue and primary hepatocytes. Using mouse genetics, we find that at the lowest concentrations of metformin that inhibit hepatic mTORC1 signaling, this inhibition is dependent on AMPK and the tuberous sclerosis complex (TSC) protein complex (TSC complex). Finally, we show that metformin profoundly inhibits hepatocyte protein synthesis in a manner that is largely dependent on its ability to suppress mTORC1 signaling.
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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.