MeDiGes Study. Metformin versus insulin in gestational diabetes: Glycemic control, and obstetrical and perinatal outcomes. Randomized prospective trial.

Abstract Background Gestational diabetes not properly controlled with diet has been commonly treated with insulin. In recent years several studies have published that metformin can lead to, at least, similar obstetrical and perinatal outcomes as insulin. Nevertheless, not all clinical guidelines endorse its use, and clinical practice is heterogeneous. Objectives The aim of this study was to test if metformin could achieve the same glycemic control as insulin and similar obstetrical and perinatal results, with a good safety profile, in women with gestational diabetes not properly controlled with lifestyle changes. Study design The MeDiGes study was a multicenter, open-label, parallel arms, randomized clinical trial performed at two hospitals in Malaga (Spain), enrolling women with GDM who needed pharmacological treatment. Women aged 18-45 years, in the second or third trimesters of pregnancy, were randomized to receive metformin or insulin (Detemir and/or Aspart). The main outcomes were: 1. glycemic control (mean glycemia, pre-prandial and postprandial) and hypoglycemic episodes, and 2. obstetrical and perinatal outcomes and complications (hypertensive disorders, type of labor, prematurity, macrosomia, large for gestational age, neonatal care unit admissions, respiratory distress syndrome, hypoglycemia, jaundice). Outcomes were analyzed on an intention-to-treat basis. Results Between 2016-October and 2019-June 200 women were randomized, 100 to the insulin-treated group and 100 to the metformin-treated group. Mean fasting and postprandial glycemia did not differ between groups, but postprandial glycemia was significantly better after lunch and/or dinner in the metformin-treated-group. Hypoglycemic episodes were significantly more common in the insulin-treated group (55.9% vs 17.7% on metformin, OR 6.118, 95% CI 3.134-11.944, p 0.000). Women treated with metformin gained less weight from the enrollment to the prepartum visit (36-37 gestational weeks) (1.35±3.21 vs 3.87±3.50 Kg, p 0.000). Labor inductions (MET 45.7% vs INS 62.5%, OR 0.506, 95% CI 0.283-0.903, p 0.029) and cesarean deliveries (MET 27.6% vs INS 52.6%, OR 0.345, 95% CI 0.187-0.625, p 0.001) were significantly lower in the MET-group. Mean birth weight, macrosomia and large for gestational age were not different between treatment groups, as well as babies’ complications. The lower cesarean delivery rate for women treated with metformin was not associated with macrosomia, large or small for gestational age, or other complications of pregnancy. Conclusions Metformin treatment was associated with a better postprandial glycemic control than insulin for some meals, a lower risk of hypoglycemic episodes, less maternal weight gain, and a low rate of failure as an isolated treatment. Most obstetrical and perinatal outcomes were similar between groups.