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Common diabetes drug helps reverse diabetic patients’ heart disease risk

In 2019, about 463 million people suffered from diabetes and over 2 million people lost their lives to its complications, including common cardiovascular complications such as heart attacks and strokes. We need to discover new ways to combat diabetes and its complications to improve the quality of life and prolong the survival of millions of patients.

High blood sugar is toxic for blood vessels and this toxic effect is believed to be responsible for the cardiovascular complications of diabetes, such as heart attacks and strokes. Insulin is a common treatment used to reduce blood sugar levels in people with diabetes – usually administered with an insulin pen or pump.

But much to scientists’ surprise, clinical trials have shown that insulin treatment doesn’t reduce the risk of heart attacks and strokes, even though it greatly reduces sugar in the bloodstream. This means that controlling blood sugar with insulin is not enough to prevent damage in the blood vessels of patients with diabetes. Why does this happen? What are we missing in this chain of events?

Diabetes patient using an insulin pen.

Insulin damages blood vessels

In our recent study, we observed that insulin itself causes oxidative damage to the human arteries, which is exactly what we try to prevent by treating diabetes. So any benefit we have from reducing blood sugar is offset by the direct damage insulin can cause to the blood-vessel wall. Ours is the first study to demonstrate this effect in humans and it contradicts previous studies performed in mice and cell-based models.

But are these negative effects of insulin on human arteries reversible? In the same study, we found that a category of anti-diabetic tablets acting as inhibitors of the enzyme dipeptidyl peptidase 4 (DPP4), can “reprogram” the response of human arteries to insulin. Indeed, when insulin is given to patients with diabetes pre-treated with a DPP4 inhibitor, it leads to a striking improvement of blood vessel health, instead of inducing oxidative damage.

DPP4 inhibitors reduce blood glucose mainly by stimulating pancreatic insulin production. Doctors use them in less severe cases of diabetes that don’t need insulin treatment. Currently, doctors don’t often tend to prescribe DPP4 inhibitors in combination with insulin.

Because our study examined insulin and DPP4 inhibitors, and both are already approved and used in diabetes, our findings are rapidly translatable to humans without the need for the further cell-based and animal studies usually needed for new drugs. This could affect the way insulin and DPP4 inhibitors are used in clinical practice very soon.

Strokes and heart attacks remain among the most common, serious and potentially life-threatening complications of diabetes. So there is an unmet need to find better, more efficient ways to treat diabetes, both by reducing blood glucose and by efficiently protecting all organs at risk, such as the heart and blood vessels.

In the meantime, the combination of insulin with a DPP4 inhibitor may prevent the cardiovascular complications of diabetes by reducing damage to the blood vessel wall caused either from high blood sugar or from insulin treatment. We now need well designed clinical trials to evaluate the clinical benefit of this regimen.

This novel idea to combine insulin with a DPP4 inhibitor could improve the quality of life for millions of people with diabetes and prevent future heart attacks and strokes.

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