Nature Middle East | House of Wisdom

How metformin works

Chris Triggle, Gnanapragasam Arunachalam and Hong Ding

Chris Triggle, Gnanapragasam Arunachalam and Hong Ding

WCMC-Q

Researchers at Weill Cornell Medical College in Qatar (WCMC-Q) have managed to understand how metformin, a widely used oral diabetes drug, interacts with the body to control the blood glucose level.

According to the researchers, metformin works on the ‘longevity gene’ SIRT1 to protect the user’s vascular system against deterioration caused by glucose toxicity.

When the researchers exposed mouse microvascular endothelial cells to high blood glucose levels, they noticed a significant reduction in the expression of SIRT1 and aging of endothelial  cells. Treating the mice with metformin countered this reduction in SIRT1 expression and protected endothelial  cells from this premature aging. However, after knockdown of SIRT1 the mice lost the protective effect produced by metformin. This suggests that the protection the drug offers for diabetes is at least partly due to its effect on the expression of SIRT1.

“The most common cause of death for diabetes patients is vascular and microvascular deterioration – it’s like an advanced aging of the vascular system – so metformin is an extremely useful drug,” said Chris Triggle, professor of pharmacology at WCMC-Q and one of the authors of the research that was published in the British Journal of Pharmacology.

He adds that metformin has long been known to reduce morbidity in patients with diabetes-associated microvascular disease, but that until now the reason for this beneficial effect had not been understood.

In the past, metformin was thought to act by reducing gluconeogenesis – or the formation of glucose from non-carbohydrate sources – in the liver, which in turn would reduce the amount of glucose in the blood and decrease vascular damage. “We realized some years ago that the reported and generally accepted mechanisms of metformin did not really fit with the pharmacokinetic profile – the way the drug interacts with the body – of the drug. Our study proves that metformin does indeed have a direct protective action on the vasculature,” said Triggle.

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    Tom Hennessy said:

    Since iron causes diabetes and metformin lowers iron, then the action of metformin in diabetes may be due to its’ lowering of body iron.
    “reduction in body iron stores with metformin”
    “improvement in insulin sensitivity and insulin secretion with frequent blood donation and decreased iron stores”
    “relationship between moderate iron overload and diabetes risk”