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Diabetes Obes Metab. 2018 Jul;20(7):1642-1651. doi: 10.1111/dom.13275. Epub 2018 Mar 26.

Safety of non-insulin glucose-lowering drugs in pregnant women with pre-gestational diabetes: A cohort study.

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Department of Public Health and Maternal and Child Health, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain.
Global Epidemiology, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut.
Corporate Department of Global Epidemiology, Boehringer Ingelheim GmbH, Ingelheim, Germany.
Hannover Medical School, Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover, Germany.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.



To evaluate the association between use of non-insulin antidiabetics in early pregnancy and the risk of miscarriages, stillbirths and major structural malformations.


A cohort of 1511 pregnant women with pre-gestational diabetes linked to live births was identified using electronic medical records from The Health Improvement Network (THIN) for the period 1995 to 2012. Information on prescriptions, foetal outcomes and potential confounders was ascertained from both codes and free text in the THIN database. Odds ratios (OR) and 95% confidence intervals (CI) of adverse foetal outcomes in women treated with non-insulin antidiabetics during the first trimester compared to those on insulin were estimated using logistic regression to adjust for type of diabetes, glycaemic control and other maternal characteristics.


Among 311 pregnant women on non-insulin antidiabetics, 21.9% had a miscarriage and 1.6% a stillbirth; 1.9% of live births had major malformations. The corresponding frequencies for the 883 women on insulin were 13.3%, 1.7% and 9.6%. Insulin users more often had type 1 diabetes and poor glycaemic control. Compared to women with type 1 diabetes, those with type 2 diabetes had a higher risk of miscarriages (20.5% vs 12.8%) but a lower prevalence of malformations (4.0% vs 9.2%). Compared to women with HbA1c ≤7%, those with HbA1c >7% had a higher prevalence of malformations (12.6% vs 2.7%). After adjustment for diabetes type and glycaemic control, compared to insulin, non-insulin antidiabetic patients were associated with an OR for miscarriage of 1.19 (95% CI, 0.75-1.89), for stillbirths of 0.65 (95% CI, 0.16-2.58), and for major malformations of 0.25 (95% CI, 0.08-0.84).


Among women with diabetes, use of non-insulin antidiabetics early in pregnancy was not associated with greater risks of foetal losses or major malformations than was insulin.


antidiabetic drugs; database research; pharmaco-epidemiology; safety; type diabetes

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