Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus

Aim: To evaluate glycemic control among women with gestational diabetes mellitus (GDM) under insulin versus metformin (with or without insulin supplementation), and to identify metformin poor responders requiring supplemental insulin. Methods: In Ain Shams University Hospital, mothers with 26-32-week GDM pregnancies, failing diet control, were randomized to receive metformin (n = 47) or insulin (n = 48). The primary outcome was glycemic control. Secondary outcomes included maternal weight, parameters predicting successful metformin monotherapy, neonatal hypoglycemia, and birthweight. Results: Women using metformin (23.4% needing supplemental insulin) gained less weight (P < 0.001), and had lower fasting glucose during the first and last 2 weeks of treatment (P = 0.014 and 0.008, respectively) when compared with insulin monotherapy. Insulin supplementation in the metformin group was related to initial body mass index, HbA1c, oral glucose tolerance test (GTT), and first week mean glucose level. The 1-h glucose level during initial GTT (Hr1-GTT) and the mean fasting glucose level during the first week of therapy (Wk1-mFG) were the two independent parameters associated with requiring supplemental insulin. Women with Hr1-GTT >212 mg/dL and Wk1-mFG >95 mg/dL had a risk ratio of 58.6 (95% CI: 3.68-933.35, P = 0.004) and 11.5 (95% CI: 2.77-47.34,= 0.0008), respectively for needing supplemental insulin during the course of the study compared with women without. Conclusion: Metformin is an effective and safe alternative to insulin in GDM. Women using metformin (+/- supplemental insulin) had similar glycemic control, less weight gain, and similar rates of side-effects as those on insulin monotherapy. Insulin supplementation to metformin therapy was more likely with elevated Hr1-GTT and Wk1-mFG.