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Metformin: A Potential Therapeutic Tool for Rheumatologists.

Authors
  • Salvatore, Teresa1
  • Pafundi, Pia Clara2
  • Galiero, Raffaele2
  • Gjeloshi, Klodian2
  • Masini, Francesco2
  • Acierno, Carlo2
  • Di Martino, Anna2
  • Albanese, Gaetana2
  • Alfano, Maria2
  • Rinaldi, Luca2
  • Sasso, Ferdinando Carlo2
  • 1 Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via de Crecchio, 7, I-80138 Naples, Italy. , (Italy)
  • 2 Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza L. Miraglia, 2, I-80138 Naples, Italy. , (Italy)
Type
Published Article
Journal
Pharmaceuticals
Publisher
MDPI AG
Publication Date
Sep 04, 2020
Volume
13
Issue
9
Identifiers
DOI: 10.3390/ph13090234
PMID: 32899806
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes, acting via indirect activation of 5' Adenosine Monophosphate-activated Protein Kinase (AMPK). Actually, evidence has accumulated of an intriguing anti-inflammatory activity, mainly mediated by AMPK through a variety of mechanisms such as the inhibition of cytokine-stimulated Nuclear Factor-κB (NF-κB) and the downregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathways. Moreover, AMPK plays an important role in the modulation of T lymphocytes and other pivotal cells of the innate immune system. The current understanding of these AMPK effects provides a strong rationale for metformin repurposing in the management of autoimmune and inflammatory conditions. Several studies demonstrated metformin's beneficial effects on both animal and human rheumatologic diseases, especially on rheumatoid arthritis. Unfortunately, even though data are large and remarkable, they almost exclusively come from experimental investigations with only a few from clinical trials. The lack of support from prospective placebo-controlled trials does not allow metformin to enter the therapeutic repertoire of rheumatologists. However, a large proportion of rheumatologic patients can currently benefit from metformin, such as those with concomitant obesity and type 2 diabetes, two conditions strongly associated with rheumatoid arthritis, osteoarthritis, and gout, as well as those with diabetes secondary to steroid therapy.

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