Brick by Brick: Metformin for Gestational Diabetes Mellitus?

Jean-Luc Ardilouze; Masoud Mahdavian; Jean-Patrice Baillargeon

Disclosures

Expert Rev Endocrinol Metab. 2010;5(3):353-357. 

In This Article

Summary of Methods & Results

Pregnant women with GDM (defined as 2-h glucose ≥7.8 mmol/l during a 75-g oral glucose tolerance test [OGTT]) at 28 weeks gestation and not controlled by lifestyle modifications, as demonstrated by self-monitoring of blood glucose (SMBG; 4 tests daily), duly consented to participate in the study and were prescribed metformin. Capillary glucose targets were less than 6.0 mmol/l (fasting) and less than 8.0 mmol/l or under 7.0 mmol/l (1- and 2-h postprandially, respectively). Metformin was titrated: subjects initially received 500 mg twice daily and dosage was adjusted weekly (maximum: 2500 mg daily). Supplementation of metformin by insulin was initiated when glycemic control was not achieved with maximal dosage.

Metformin was prescribed to 127 subjects; but the study was not intent-to-treat and 27 women were excluded from analyses: 13 because insulin was required and 14 because of side effects or low compliance. The remaining 100 women, exclusively treated with metformin, were compared with a retrospective cohort of 100 women treated with insulin therapy (a basal-bolus regimen of aspart and glargine). Care was delivered to both groups at the same hospital, by the same team using the same SMBG targets. At baseline, groups were similar in ethnicity (43% Asians and Africans in the metformin group vs 48% in the insulin group), age (34.2 vs 33.9 years), reported pregestational BMI (30.4 vs 30.5 kg/m2), family history of diabetes (50 vs 57% of subjects) and HbA1c at entry (5.5 vs 5.7%); however, subjects in the insulin group reported more previous GDM (13 vs 25%; p = 0.05) and tended to have higher fasting glucose at diagnosis (4.8 vs 5.5 mmol/l; p = 0.06). The median daily dose of metformin was 1500 mg (range: 1000–2000 mg) for a median duration of 7 weeks (range: 1–25 weeks). Insulin was used for 8 weeks (range: 2–24 weeks).

In mothers, mean gain in weight from enrolment to term was lower in the metformin group (0.94 vs 2.72 kg; p < 0.01). Percentage of hypertensive disorders of pregnancy (HDP; e.g., gestational hypertension, preeclampsia and proteinuria) were not statistically different (6 vs 7%, 2 vs 9% and 9 vs 11%, respectively) between groups. Induction of labor (26 vs 24%), cesarean delivery (48 vs 52%) and term delivery (100 vs 90%) were not different either, while prematurity (delivery <37 weeks gestation) was higher in the insulin group (0 vs 10%; p < 0.01).

In neonates, except for three outcomes favorable to metformin (e.g., lower mean birthweight centile for gestational age; 44.6 vs 56; p < 0.01), reduced percentage of phototherapy required for jaundice (8 vs 30%), and admissions in intensive care unit (6 vs 19%; p < 0.01), other perinatal outcomes were not statistically different between groups: mean birth weight, macrosomia, small-for-gestational-age neonates, respiratory distress, congenital anomalies, and shoulder dystocia. Hypoglycemia (defined as glucose <2.6 mmol/l within 2 h after birth) tended to be less frequent in the metformin group (9 vs 18; p = 0.09), although this difference reached statistical significance when patients requiring insulin in the metformin group were included in the analyses. No perinatal death was recorded.

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