Merck KGaA’s Glucophage approved in Europe as first oral diabetic medication for use during pregnancy

Merck KGaA – known as EMD Serono in the US and Canada – has announced in a European work-sharing procedure (WSP) that an extension to the label for metformin products in the EU has been approved – including Glucophage (metformin hydrochloride HCL immediate release), Glucophage XR (metformin HCL extended release) and Stagid (metformin embonate immediate release).

The decision allows Glucophage to be used as the first oral anti-diabetic medicine safely from conception to birth and addresses an unmet medical need regarding the prevalence of hyperglycaemia. In 2021, 21.1 million births were affected by hyperglycaemia worldwide.

The European Health authorities participating in the WSP analysed the potential risk and benefit factors of metformin when used on both the mother and child, with the decision based on data – taken from Merck’s own safety cohort study CLUE1 and a substantial body of evidence – evaluating metformin in pre-gestational and gestational diabetes.

For the mother, metformin was better than insulin regarding pregnancy weight gain and was also comparable to insulin in reaching maternal blood sugar control.

When used during pregnancy, metformin showed a lower risk of pregnancy-induced preeclampsia and hypertension and, when used together with insulin for pre-gestational diabetes, metformin significantly reduced the amount of insulin needed, while lowering the risk of chronic hypoglycaemia.

A vital part of the study was confirming how metformin crosses the placenta and the impact this could have on the safety of the unborn child. Babies exposed to metformin in utero may have a lower birth weight than those exposed to insulin but are less likely to be at risk of a severe blood sugar dip straight after birth.

As yet, no long-term dangers for the child in later life – for example, negative impacts on mental development and weight – have been confirmed. In some cases, metformin alone is not enough to control blood sugar levels. In these instances, it is advisable for doctors to use metformin in combination with insulin, or change to insulin.

Maria Rivas, senior vice president and chief medical officer at Merck said: “During pregnancy and when wanting to become pregnant, good glycemic control is of utmost importance, as insufficient glycaemic control leads to a three times higher risk of pregnancy loss than in normoglycemic women. The estimated risk of malformation is doubled.

“Until now, pregnant women were required to use insulin to control their blood sugar during this period. The label extension now opens a tablet alternative to women who are not able or wanting to use daily injections.”