ArticleScientific reports2021
Metformin selectively dampens the acute inflammatory response through an AMPK-dependent mechanism.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.The New England journal of medicine · 2022Trial
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Macrophage-driven pathological ossification of the posterior longitudinal ligament: mechanistic insights and therapeutic opportunities.Bone research · 2026Review
- Metformin and Severe Post-COVID-19 Outcomes Among Individuals with Diabetes Mellitus.medRxiv : the preprint server for health sciences · 2026Article
- Elevated placental inflammation as a mediator of adverse outcomes in gestational diabetes mellitus.Molecular and cellular biochemistry · 2026Article
- The Yin and Yang of cellular senescence in ischemia-induced myocardial injury.Trends in cardiovascular medicine · 2026Review
- Reactive oxygen species and metabolic checkpoints shape plasmacytoid dendritic cell fate in infection and autoimmunity.Redox biology · 2026Review
- Ulcerative colitis, pathophysiological mechanisms and drug repurposing: a new therapeutic dawn-narrative review.Inflammopharmacology · 2026Review
- Effect of Metformin on the Risk of Post-COVID-19 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- The central role of IL-6 in the differential effects of GLP-1 receptor agonists and metformin across multiple health conditions.Frontiers in immunology · 2026Review
- The role of immune regulation in peripheral nerve regeneration: functions of inflammatory cells and cytokines.Frontiers in pharmacology · 2026Review
- Biguanides are associated with decreased early mortality and risk of acute kidney injury in hospitalised patients with COVID-19: a nationwide retrospective cohort study in Japan.Clinical and experimental nephrology · 2026Article
- Metformin Mitigates Diabetes-Driven Renal Senescence via Immunomodulation and the FABP4/FOXO1 Axis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.Biomolecules · 2025Review
- Enrichment and functional characterization of copper-binding peptides from food hydrolysates.RSC advances · 2025Article
- Article
- In Vitro Treatment with Metformin Significantly Reduces Senescent B Cells Present in the Adipose Tissue of People with Obesity.The Journal of nutrition · 2025Article
- The adjunctive role of metformin in patients with mild to moderate ulcerative colitis: a randomized controlled study.Frontiers in pharmacology · 2025Article
- Article
- Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Metformin is a first-line drug in the treatment of type-2 diabetes mellitus (T2DM). In addition to its antigluconeogenic and insulin-sensitizing properties, metformin has emerged as a potent inhibitor of the chronic inflammatory response of macrophages. In particular, metformin treatment has been shown to reduce expression of interleukin (IL-) 1β during long-term exposure to the pro-inflammatory stimulus lipopolysaccharide (LPS) through a reduction in reactive oxygen species (ROS), which decreases the levels of the hypoxia-inducible factor (HIF) 1-α, and through enhanced expression of IL-10. However, the effect of metformin on the acute inflammatory response, before significant levels of ROS accumulate in the cell, has not been explored. Here, we show that metformin alters the acute inflammatory response through its activation of AMP-activated protein kinase (AMPK), but independently of HIF1-α and IL-10, in primary macrophages and two macrophage-like cell lines. Thus, metformin changes the acute and the chronic inflammatory response through fundamentally distinct mechanisms. Furthermore, RNA-seq analysis reveals that metformin pretreatment affects the levels of a large yet selective subset of inflammatory genes, dampening the response to short-term LPS exposure and affecting a wide range of pathways and biological functions. Taken together, these findings reveal an unexpected complexity in the anti-inflammatory properties of this widely used drug.
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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.