Should Metformin Replace Insulin for Gestational Diabetes?

Should Metformin Replace Insulin for Gestational Diabetes?
Should Metformin Replace Insulin for Gestational Diabetes?

Gestational diabetes mellitus (GDM) is a common medical complication of pregnancy1 and is associated with several adverse outcomes, including increased maternal risk for preeclampsia, cesarean section, development of type 2 diabetes (T2D) after pregnancy, and increased risk for neonatal death, stillbirth, congenital defects, macrosomia, shoulder dystocia during delivery, and neonatal hypoglycemia directly after birth.2 

The incidence of T2D-induced pregnancy complications is rising—due in part to the obesity epidemic—with approximately 1% to 14% of all pregnancies complicated by GDM (depending on the population studied and the diagnostic tests employed) and resulting in 200,000 cases annually.1

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Management of GDM is primarily aimed at controlling glycemic levels and can involve several interventions, including dietary therapy, exercise, oral hypoglycemic agents, or insulin.3 Typically, treatment is initiated with exercise and diet,4 but subcutaneous insulin therapy may be added if these measures do not bring adequate glycemic control.5  

Drawbacks to insulin therapy include risk of hypoglycemia and maternal weight gain, the necessity of multiple daily injections, and regular adjustment based on the patient's body mass index (BMI), glucose levels, and lifestyle.6 An oral alternative to insulin that would achieve similar glycemic control without these drawbacks could represent an important improvement in the treatment of GDM.7

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Metformin, a first line medication for T2D, has garnered attention as a potential candidate for filling this role.2 But because of its high maternal-to-fetal transfer rate (10% to 16%), which might be associated with fetal abnormalities as well as potential adverse effects for mothers and newborns after delivery, it has not been widely used in GDM.2 

Research findings have been mixed and study quality has been inconsistent. A recent meta-analysis of five trials consisting of 1270 participants9,10,11,12 involving GDM and metformin sought to shed light on the "controversial" use of metformin by comparing it to insulin in terms of glycemic control, as well as maternal and neonatal outcomes in GDM.2

Study Results

The researchers found both beneficial and problematic effects of metformin. Data regarding average weight gain after were available from three trials. Average weight gains were much lower in the metformin than in the insulin group (n = 1006, P = 0.003, SMD = −0.47, 95%CI [−0.77 to −0.16]). The incidence of pregnancy-induced hypertension was also significantly less in the metformin group (n = 1110, P = 0.02, OR = 0.52, 95%CI [0.30 to 0.90]). 

The fasting blood sugar levels of oral glucose tolerance test (OGTT) were significantly lower in the metformin group than in the insulin group (n = 478, P = 0.0006, SMD = −0.83, 95%CI [−1.31 to −0.36]). There was no significant difference in the preeclampsia rate between the two groups (n = 1110, P = 0.13, OR = 0.69, 95%CI [0.42 to 1.12]).

But the impact of metformin on neonatal outcomes was mixed. Average birth weights were slightly lower in the metformin group, as compared with the insulin group, but the difference was not statistically significant (5 studies, n = 1270, P = 0.54, SMD = −0.04, 95%CI [−0.17 to 0.09]).