Safety of non-insulin anti-diabetes drugs in early pregnancy

This study compared the safety of non-insulin anti-diabetes drugs (NIADD) to insulin in early pregnancy in women with diabetes diagnosed before pregnancy. It was determined that NIADD did not increase the risk of miscarriages, stillbirths, or major structural anomalies compared to insulin.

Women with diabetes have a higher risk of complications in pregnancy, like miscarriage and stillbirth, than women without diabetes. Lowering blood glucose levels before pregnancy and in early pregnancy can reduce the risk of these complications. Metformin (Glucophage) and glyburide (Glibenclamide) are NIADDs that may be as safe and effective as insulin in late pregnancy. However, less is known about the risks, if any, of NIADDs during early pregnancy.

Information on 1,511 pregnant women with diabetes was collected from a database in the United Kingdom. 907 had type 1 diabetes (T1D) and 604 had type 2 diabetes (T2D). Information about their treatment and their pregnancy was collected. They were also compared to 10,000 pregnant women without diabetes.

Miscarriages were more common in women with diabetes (15.9%) than without diabetes (10.5%). Stillbirths were also more common in women with diabetes (1.5%) than without diabetes (0.4%). The children of women with diabetes were more likely to have major structural anomalies (7.4%) than the children of women without diabetes (2.8%). The most common abnormalities were heart-related.

311 of the women with diabetes were treated with NIADD in early pregnancy. 883 were treated with insulin only. Miscarriages occurred in 21.9% of the NIADD group and 13.3% of the insulin group. However, after taking factors like age, weight, and type of diabetes into account, the risk of miscarriage was similar in both groups. Stillbirths occurred at similar rates in both groups. The children of women trated with NIADD were 75% less likely to have major structural anomalies than those treated with insulin.

Women with T1D were 32% less likely to have a miscarriage than women with T2D. The children of women with T1D were 3.21 times more likely than those of women without T2D to have a major structural anomaly. The rates of stillbirth were similar for women with T1D and T2D.

Pre-pregnancy HbA1c levels (average blood glucose over the last 3 months) did not affect the risk of miscarriage or stillbirths. However, children of women with HbA1c levels greater than 7% before pregnancy were 4.29 times more likely to have major structural anomalies than the children of women with HbA1c levels less than 7%. HbA1c levels during the first trimester did not influence the risk of stillbirth or major structural anomalies. However, women with HbA1c levels greater than 7% in the first trimester were 2.26 times more likely to have a miscarriage than women with HbA1c levels less than 7%.

The study concluded that NIADDs do not increase the risk of stillbirth or miscarriage, but may reduce the risk of major structural anomalies, compared to insulin. It was also determined that women with T1D were less likely to have a miscarriage, but more likely to have a major structural anomaly in their child. HbA1c levels, before and during the first trimester, affected the risk of major structural anomalies, and miscarriage, but not stillbirths.

This study was funded by a manufacturer of a NIADD. Some information, such as the cause of stillbirth, was missing from the database. Furthermore, the effects of different kinds of NIADDs were not compared to each other.

Discuss the use of NIADDs in pregnancy with your physician.