(573) Does metformin use in pregnancy alter glucose tolerance postpartum in patients with gestational diabetes?

Animal studies suggest use of metformin in pregnancy may increase insulin resistance during pregnancy and postpartum. We aimed to investigate the association between treatment of GDM with metformin vs insulin and the incidence of dysglycemia postpartum.

Study Design:
A retrospective cohort was conducted using the United States Collaborative Network in TriNetX. Patients aged 18 to 50 with a diagnosis of medication controlled GDM after 24 weeks gestation were included. Two groups were defined as GDM with metformin and GDM with insulin. Cohorts were matched for age, race, ethnicity, BMI, and primary hypertension (HTN). The primary outcome of dysglycemia was assessed at 1 to 2 years after pregnancy and defined by laboratory measurements (HbA1C, 2-hour oral glucose tolerance testing, and fasting glucose) and ICD-10 codes for diabetes and prediabetes. Other outcomes of interest included HTN, hyperlipidemia, and cardiovascular disease postpartum. Logistic regression was performed to determine odds ratios (OR) and 95% confidence intervals (CI).

Results:
After matching, there were 10,362 individuals in each group. Individuals with a metformin prescription were more likely to develop prediabetes at 1 to 2 years postpartum based on ICD-10 codes (4.5% vs 2.2%, OR 2.06 (CI 1.75, 2.42)) and laboratory diagnosis (5.4% vs 3.8%, OR 1.45 (CI 1.27, 1.65)) compared to those prescribed insulin alone (Table 1). The risk of developing diabetes based on ICD-10 codes (OR 1.04 (CI 0.92, 1.18)) and laboratory diagnosis (OR 0.94 (CI 0.75, 1.16)) was not different between groups. There was also an increased risk of hyperlipidemia (3.8% vs 2.5%, OR 1.5 (CI1.29, 1.78)) among the metformin group, though no difference in diagnosis of HTN.

Conclusion:
Treatment with metformin during a pregnancy complicated by GDM is associated with an increased risk of developing prediabetes 1 to 2 years after pregnancy. This could suggest metformin use in pregnancy may impact glucose tolerance beyond pregnancy. Further investigation is warranted to explore potential residual confounding and physiologic mechanism.