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P13 Anti-inflammatory effects of metformin – useful in cardiovascular disease?
  1. AR Cameron1,
  2. M Mohan1,
  3. Calum Forteath1,
  4. AD McNeilly1,
  5. DJK Balfour1,
  6. A Wong1,
  7. M Foretz2,3,4,
  8. CC Lang1,
  9. G Rena1
  1. 1Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
  2. 2INSERM U1016, Institut Cochin
  3. 3CNRS UMR8104
  4. 4Université Paris Descartes, Sorbonne Paris Cité, Paris, France

Abstract

Background Metformin is the first line drug treatment for type 2 diabetes (T2D). Along with its anti-hyperglycaemic properties, metformin is also associated with beneficial effects in cardiovascular disease (CVD). In observational studies, metformin has been associated with fewer adverse CV events.1 How metformin induces these effects is unclear as its mechanism of action is still to be determined. Inflammation, including NF-κB signalling, has been recognised as a contributing factor to both diabetes and CVD with metformin recently reported to have effects upon inflammatory signalling.2,3 In this study, we have utilised primary cells and human plasma to investigate the anti-inflammatory effects of metformin and how this may be useful in CVD.

Results In mouse hepatocytes, TNFα-dependent IκB degradation and expression of pro-inflammatory mediators were inhibited by metformin and the IKKβ inhibitor BI605906. These effects upon NF-κB signalling could be separated from metabolic effects as BI605906 did not replicate metformin’s actions upon lipogenic gene expression, glucose production or AMPK activation. Analysing the plasma from a non-diabetic heart failure cohort,4 metformin use was associated with suppression of several plasma cytokines.

Conclusion This study has demonstrated that the anti-inflammatory effects of metformin are separate from its anti-hyperglycaemic actions. This knowledge indicates that metformin may be harnessed for use in ‘at risk’ CVD groups irrespective of diabetes status.

References

  1. Evans, et al. Diabetologia 2006;49:930–6

  2. Isoda, et al. Arteriosclerosis, Thrombosis, and Vascular Biology 2006;26:611–7

  3. Woo, et al. PLoS One 2014;9:e91111

  4. Wong, et al. European Journal of Heart Failure 2012;14:1303–10

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