Histopathological lesions of the placenta in pregnancies affected by diabetes: A correlation between metformin versus insulin

Abstract

Background: The global rise in diabetes prevalence during pregnancy is contributing to increased maternal and neonatal morbidity. While metformin effectively controls glycemia in both type 2 diabetes and gestational diabetes mellitus (GDM) and offers practical benefits compared to insulin, its widespread adoption as a first-line treatment is constrained by concerns over placental transfer and potential impacts on placental function, fetal development and offspring's long-term health effects. Objective: This study aims to assess the association between maternal diabetes pharmacological therapy (metformin versus insulin) and placental histopathology in term singleton pregnancies. Methods: A retrospective study was conducted of term singleton diabetic pregnancies delivered from January 2019 to October 2023. Maternal and neonatal electronic medical records along with placental histopathology reports were reviewed, identifying 105 pregnancies that met the inclusion criteria (59 treated with metformin and 46 with insulin). Placental lesions were categorized based on the 2014 Amsterdam Consensus. Relevant gestational clinical data, primary neonatal outcomes, and placental histological lesions were compared between the two treatment groups. Results: Maternal anthropometric profiles and comorbidities were comparable between the treatment groups, with the exception of a higher prevalence of pre-gestational obesity in the metformin group and a significantly increased rate of thyroid disease during pregnancy in the insulin group. Women in the insulin group exhibited significantly higher glycated hemoglobin (HbA 1c) levels during pregnancy compared to those in the metformin group. There were no significant differences in neonatal complications associated with diabetes in either type 2 or gestational diabetes cases. However, pregnancies with type 1 diabetes, which were managed exclusively with insulin, demonstrated greater maternal gestational weight gain, higher rates of large-for-gestational-age neonates, and elevated fetoplacental weight ratios. Chronic deciduitis was the only placental lesion significantly more frequent in the metformin group among cases of gestational diabetes.