A commonly prescribed drug for the treatment of cancer may also be useful in tackling diabetes, according to new research published online in the journal Nature Medicine.
Aflibercept, which is marketed as Eylea or Zaltrap, is a relatively cheap drug used to treat metastatic colorectal cancer and a form of the eye condition macular degeneration.
It works by blocking the growth of blood vessels into tumours and starving them of oxygen, and is a member of a family of proteins that inhibit the vascular endothelial growth factor (VEGF) pathway – a pathway which scientists have found is involved in the development of diabetes.
Researchers at Stanford University in California conducted two mice-based studies which they say explain an observation made several years ago that VEGF inhibitors, such as aflibercept, could reduce blood glucose levels in mice.
Dr Calvin Kuo, senior author of one of the studies, said: “We were surprised to find this drug currently used in patients for cancer treatment had beneficial effects on diabetes in laboratory mice and could potentially in humans.”
According to the scientists, hypoxia (lack of oxygen) induces a protein known as HIF-2alpha. This protein activates the expression of insulin receptor substrate 2 (IRS2), which in turn improves the ability of cells in the liver to respond to insulin, the hormone responsible for regulating blood glucose levels.
In the studies, treatment of normal and diabetic laboratory mice with a variety of VEGF inhibitor drugs, including aflibercept, caused the regression of blood vessels and boosted the number of hypoxic cells in the liver. This led to an increase in HIF-2alpha levels and IRS2 expressio, and as a result made the animals better at tolerating rises in blood glucose.
Dr Kuo concluded: “Much work remains to translate these mouse studies to human patients, but it will be interesting to explore VEGF inhibitors or drugs that can stabilize HIF-2alpha, such as prolyl hydroxylase inhibitors, for diabetes treatment.”

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