ArticleAnnals of the rheumatic diseases2020
Metformin limits osteoarthritis development and progression through activation of AMPK signalling.
Article in Annals of the rheumatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 178 papers, 2 of them syntheses that pooled it.
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Who cites it
178 citing papers in PubMed, 2 syntheses or guidelines pooled it, 289 citations in OpenAlex.
- Metformin for knee osteoarthritis in overweight and obese adults: a systematic review and meta-analysis of efficacy, safety, and disease-modifying anti-inflammatory potential.Inflammopharmacology · 2026Pooled it
- Effectiveness of metformin in the management of osteoarthritis in patients with type 2 diabetes.Clinical rheumatology · 2026 · on this mapPooled it
- Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA.Arthritis research & therapy · 2023Trial
- Emerging therapies for knee osteoarthritis.Nature reviews. Rheumatology · 2026Review
- Dose-dependent histopathological and immunohistochemical effects of metformin in experimental osteoarthritis.Clinical rheumatology · 2026Article
- Endocrine‑metabolic imbalance drives osteoarthritis: From whole‑joint pathobiology to precision therapy (Review).International journal of molecular medicine · 2026Review
- Metabolic disorders and osteoarthritis: novel insights into pathological mechanisms and therapeutic strategies.Life medicine · 2026Review
- Association of metformin with osteoarthritis progression and total joint arthroplasty: evidence from the UK Biobank, a large population-based cohort study.Clinical rheumatology · 2026Article
- Pathological mechanisms of osteoarthritis in the network of geriatric comorbidities: Emerging insights from organs-crosstalk.Journal of orthopaedic translation · 2026Review
- Semaglutide alleviates osteoarthritis independent of weight loss via GLP-1R-mediated activation of autophagy through AKT/mTOR inhibition.Journal of orthopaedic translation · 2026Article
- Novel therapeutic strategies for osteoarthritis: from mechanistic insights to precision medicine.Bone research · 2026Review
- Targeting the SARM1-cADPR-CaArthritis research & therapy · 2026Article
- Smart Nanodelivery Systems for Immunometabolic Modulation in Osteoarthritis.Exploration (Beijing, China) · 2026Review
- The transcriptional atlas, intercellular communication, and metabolic reprogramming of the cartilage and synovium in osteoarthritis patients with diabetes mellitus : a multiomics study.Bone & joint research · 2026Article
- Systemic implications of osteoarthritis: from local degeneration to systemic metabolic Dysregulation.Journal of translational medicine · 2026Review
- The role of the AMPK/NLRP3 axis in osteoarthritic bone marrow lesions of the knee: from molecular mechanisms to clinical applications.Journal of molecular histology · 2026Review
- Metformin use and the risk of incident osteoarthritis among individuals with diabetes: a register-based nested case-control study.BMJ open · 2026Article
- Empagliflozin Alleviates Osteoarthritis Progression by Attenuating Inflammation, Restoring Impaired Autophagy, and Ameliorating Chondrocyte Senescence.Biomedicines · 2026Article
- Dapagliflozin regulates chondrocyte homeostasis and protects against osteoarthritis via targets AMPKα and SGLT2.Cell death discovery · 2026Article
- Glibenclamide attenuates osteoarthritis by suppressing NLRP3 inflammasome activation in synovial macrophages through the MAPK pathway.Journal of translational medicine · 2026Article
118 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection:2020
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
objectivesIn this study, we aim to determine the effect of metformin on osteoarthritis (OA) development and progression.
methodsDestabilisation of the medial meniscus (DMM) surgery was performed in 10-week-old wild type and AMP-activated protein kinase (AMPK)α1 knockout (KO) mice. Metformin (4 mg/day in drinking water) was given, commencing either 2 weeks before or 2 weeks after DMM surgery. Mice were sacrificed 6 and 12 weeks after DMM surgery. OA phenotype was analysed by micro-computerised tomography (μCT), histology and pain-related behaviour tests. AMPKα1 (catalytic alpha subunit of AMPK) expression was examined by immunohistochemistry and immunofluorescence analyses. The OA phenotype was also determined by μCT and MRI in non-human primates.
resultsMetformin upregulated phosphorylated and total AMPK expression in articular cartilage tissue. Mild and more severe cartilage degeneration was observed at 6 and 12 weeks after DMM surgery, evidenced by markedly increased Osteoarthritis Research Society International scores, as well as reduced cartilage areas. The administration of metformin, commencing either before or after DMM surgery, caused significant reduction in cartilage degradation. Prominent synovial hyperplasia and osteophyte formation were observed at both 6 and 12 weeks after DMM surgery; these were significantly inhibited by treatment with metformin either before or after DMM surgery. The protective effects of metformin on OA development were not observed in AMPKα1 KO mice, suggesting that the chondroprotective effect of metformin is mediated by AMPK signalling. In addition, we demonstrated that treatment with metformin could also protect from OA progression in a partial medial meniscectomy animal model in non-human primates.
conclusionsThe present study suggests that metformin, administered shortly after joint injury, can limit OA development and progression in injury-induced OA animal models.
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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.