Safety of metformin use during the first trimester

We read Dr Kelly and colleagues’ article¹ along with Dr Harris’s editorial² with great interest and considered it prudent to present data from a recent meta-analysis conducted by the Motherisk Program at the Hospital for Sick Children in Toronto, Ont.

Our data, presented at the 2005 annual meeting of the Canadian Society for Clinical Pharmacology, are encouraging with respect to the safety of metformin use in the first trimester of pregnancy. In performing a meta-analytic summary, which included eight studies (only five of which could be analyzed statistically), we found an odds ratio of 0.50. Examining the numbers showed three malformed babies among the 172 cases in the exposed group. There were 17 among 236 in the control group. Examining all the data available on pregnancy outcomes (including those not included in the meta-analysis due to lack of controls), we arrived at an overall malformation rate of 1.01% in 496 first-trimester exposures, which is well within what we would expect to find in the general population.

Our results also present the possibility of a protective effect of metformin during the first trimester. It is biologically possible that, by reversing insulin resistance, metformin does protect against malformation. Although our data are encouraging, it is important to note that we examined only major malformations. This being said, our study does encourage future research into the safety of metformin during the first trimester of pregnancy.