Oral Antidiabetic Agents in Pregnancy and Lactation: A Paradigm Shift?

Denice S Feig, MD MSc; Gerald G Briggs, BPharm; Gideon Koren, MD FABMT FRCP MBBS

Disclosures

The Annals of Pharmacotherapy. 2007;41(7):1174-1180. 

In This Article

Abstract and Introduction

Abstract

Objective: To provide information on the use of oral antidiabetic agents in pregnancy and breast-feeding.
Data Sources: Primary articles were identified by a MEDLINE search (1966-March 2007) using the MeSH headings: pregnancy in diabetics, pregnancy, polycystic ovary syndrome, hypoglycemic agents, glipizide, glyburide, metformin, rosiglitazone, pioglitazone, clinical trial, controlled clinical trial, multicenter study, randomized controlled trial, case-control studies, and cohort studies.
Study Selection and Data Extraction: All studies using oral antidiabetic agents in pregnancy were evaluated and relevant data were included in the discussion.
Data Synthesis: Studies of glyburide and glipizide have found little or no transfer of these drugs across the placenta, whereas metformin and rosiglitazone cross readily. Animal studies have found no evidence to suggest that glyburide, glipizide, metformin, or rosiglitazone are teratogenic. In gestational diabetes, glyburide was safe and efficacious; however, 16-19% of women failed to achieve optimal glucose control. No developmental toxicity in infants was observed when metformin was used before and throughout pregnancy in women with polycystic ovarian syndrome (PCOS). Some of the studies involving patients with type 2 diabetes had methodological problems. A randomized controlled trial using metformin for gestational diabetes in the third trimester is underway. The human information is inadequate to evaluate the risk of glipizide or the thiazolidinediones in pregnancy. In breast milk, 3 studies measured nonsignificant amounts of metformin and one study was unable to detect either glyburide or glipizide.

Conclusions: Neither glyburide nor metformin has caused developmental toxicity in humans. Glyburide has been used for the treatment of gestational diabetes, and metformin has been used in women with PCOS who eventually became pregnant. Additional trials are needed to better define the benefits and risks of oral antidiabetic agents in pregnancy. Metformin, glyburide, and glipizide appear to be compatible with breast-feeding.

Introduction

Insulin has long been the mainstay of treatment for women with gestational diabetes and type 2 diabetes in pregnancy. Although oral antidiabetic agents (OAAs) were used in these patients in the 1970s and 1980s, concerns arose from some studies that found increased rates of perinatal mortality and neonatal hypoglycemia.[1,2,3,4,5,6] Because of these concerns, the use of OAAs in pregnancy was strongly discouraged. However, more recent data on oral agents in women with gestational diabetes and polycystic ovarian syndrome (PCOS) suggest that an important paradigm shift is occurring regarding their use in pregnancy.

The objective of this review was to examine the recent evidence regarding the safety of oral agents in pregnancy and lactation, including their transfer across the placenta or into breast milk, possible teratogenicity, and potential developmental consequences of drug exposure.

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