Use of Metformin in Pregnancy   (May 14, 2011)

Metformin as well as every other prescription drug has a "label" (in the US, called a "United States package insert" or USPI, and in Europe called the "Summary of Product Characteristics" or SPC). The label spells out what governmental agencies authorize drug companies to say about the good and bad of their prescription drugs. Labels vary from country to country depending on local laws, but the label seems always to contains a section concerning the use of the medication in pregnancy.

Drug companies and the regulators negotiate every word in a label for a new medication, as getting additional good information into the label is viewed as a marketing advantage (and vice versa for bad information). For older drugs such as metformin, which are available as generics and which are sold by several companies, there frequently is less financial incentive to update the label, and labeling may be similar or identical across all the generic versions of the drug.

Recently, the on-line version of the British newspaper The Daily Mail published an story with the intriguing title Obese mothers-to-be get a pill to prevent fat babies in NHS that surprised me when the writer implied something about the label for metformin which struck me as incorrect.

The writer was discussing a forthcoming study of 400 obese pregnant women, half of whom will receive metformin to see if it might decrease the birthweight of the newborns compared to the other half, who will receive placebo. This study seems to be a component of a larger similar study that is described in ClinicalTrials.gov, Metformin in Obese Non-diabetic Pregnant Women. This study, also in the UK, which shares the same study design and same primary endpoint of evaluating birth weight.

The reason I was surprised when I read about this study was one word, a very specific statement by the writer of the newspaper story: " Metformin... is cleared for the treatment of diabetes in pregnancy." "Cleared" was the word: to me, this strongly implies that the drug has been cleared by regulatory authorities for this indication -- which was news to me: until now, I had been unaware of any regulatory agency, in the US or Europe or elsewhere, that has approved the use of metformin in diabetic pregnant women. 

Since this is a British news story, commenting on a British study, I decided to look at some of the British labels that are available at the British website, electronic Medicines Compendium (eMC), which contains information about UK licensed medicines. It rapidly became obvious that the British regulatory authorities who approve labeling information do not encourage the use of metformin in pregnancy: "When the patient plans to become pregnant and during pregnancy, diabetes should not be treated with metformin but insulin should be used to maintain blood glucose levels as close to normal as possible in order to lower the risk of foetal malformations associated with abnormal blood glucose levels." And a Patient Information Leaflet at the same eMC website admonishes British mums and mums-to-be as follows: "Do not take Metformin if: ...you are pregnant, planning to get pregnant or are breast-feeding."

U.S. labels (available at fda.gov) are a bit more lenient in their wording, stating that insulin should be used during pregnancy, but metformin might be used: "Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Because animal reproduction studies are not always predictive of human response, [metformin] should not be used during pregnancy unless clearly needed. There are no adequate and well-controlled studies in pregnant women with [metformin]." Well, maybe that means metformin is okay to use, but physicians are reminded that metformin hasn't been studied in "adequate and well-controlled studies in pregnant women."

I don't think it's appropriate to write that metformin is "cleared" for the treatment of diabetes in pregnancy when the writer of the news story had only to fact-check the UK labels for metformin to find that it's not.

And readers of that news story should have been informed that insulin is still the treatment of choice during diabetic pregnancies.