From the Guidelines
Metformin has been found to exhibit anti-inflammatory properties, in addition to its glucose-lowering effects, as it reduces systemic inflammation by inhibiting the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) 1.
Key Points
- At typical therapeutic doses of 1000-2000mg per day, metformin has been shown to reduce systemic inflammation in patients with type 2 diabetes 1.
- The anti-inflammatory effects of metformin are thought to be mediated through the activation of adenosine monophosphate-activated protein kinase (AMPK), which has been observed in various studies 1.
- Metformin also decreases the expression of tumor necrosis factor-α and inhibits hepatic fat accumulation and glucose excretion by activating adenosine monophosphate-activated protein kinase 1.
- Long-term use of metformin (more than 6 years) in patients with diabetes mellitus and histologically proven nonalcoholic steatohepatitis (NASH) or advanced fibrosis has been shown to lower the risk of overall mortality, liver transplant, and hepatocellular carcinoma (HCC) 1.
From the Research
Anti-Inflammatory Properties of Metformin
- Metformin has been shown to have anti-inflammatory properties, with studies suggesting that it can reduce chronic inflammation by improving metabolic parameters such as hyperglycemia, insulin resistance, and atherogenic dyslipidemia 2, 3.
- The anti-inflammatory action of metformin is thought to be mediated by the inhibition of nuclear factor κB (NFκB) via AMP-activated protein kinase (AMPK)-dependent and independent pathways 2, 3.
- Metformin has been found to suppress inflammatory response, with several local and systemic anti-inflammatory effects described, including the inhibition of mTOR and NF-κB pro-inflammatory signalling cascades 3.
Mechanisms of Action
- Metformin's mechanism of action involves the suppression of endogenous glucose production, primarily by the liver, and the increase of glucose uptake in muscle 4, 5.
- Activation of AMP-activated protein kinase (AMPK) plays an important role in metformin's antihyperglycemic action, and is also involved in its anti-inflammatory effects 2, 3, 5.
- Metformin has been found to have pleiotropic actions, including an impact on plasma lipid profile, decrease of oxidative stress, and increase in plasma fibrinolytic activity 5.
Clinical Implications
- Metformin's anti-inflammatory properties may have clinical implications for the treatment of conditions such as cardiovascular disease, polycystic ovary syndrome, and cancer 2, 3, 6.
- Further studies are needed to confirm the additional benefits of metformin in these conditions, as well as its potential use in other diseases such as immunological disorders and cognitive disorders 6.