BackgroundMetformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking. MethodsWe randomly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin (with supplemental insulin if required) or insulin. The primary outcome was a composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity. The trial was designed to rule out a 33% increase (from 30% to 40%) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin. Secondary outcomes included neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment. ResultsOf the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 0.99; 95% confidence interval, 0.80 to 1.23). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin. ConclusionsIn women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment. (Australian New Zealand Clinical Trials Registry number, 12605000311651.) The New England Journal of Medicine Downloaded from nejm.org at UQ Library on March 30, 2017. For personal use only. No other uses without permission.Demographic and clinical data were recorded at enrollment. Blood samples were obtained after an overnight fast to assess baseline glycemia and to ensure that the results of renal-and liver-function tests did not preclude the use of metformin. Glu-The New England Journal of Medicine Downloaded from nejm.org at UQ Library on March 30, 2017. For personal use only. No other uses without permission.

OBJECTIVEIn women with gestational diabetes mellitus, who were randomized to metformin or insulin treatment, pregnancy outcomes were similar (Metformin in Gestational diabetes [MiG] trial). Metformin crosses the placenta, so it is important to assess potential effects on growth of the children.RESEARCH DESIGN AND METHODSIn Auckland, New Zealand, and Adelaide, Australia, women who had participated in the MiG trial were reviewed when their children were 2 years old. Body composition was measured in 154 and 164 children whose mothers had been randomized to metformin and insulin, respectively. Children were assessed with anthropometry, bioimpedance, and dual energy X-ray absorptiometry (DEXA), using standard methods.RESULTSThe children were similar for baseline maternal characteristics and pregnancy outcomes. In the metformin group, compared with the insulin group, children had larger mid-upper arm circumferences (17.2 ± 1.5 vs. 16.7 ± 1.5 cm; P = 0.002) and subscapular (6.3 ± 1.9 vs. 6.0 ± 1.7 mm; P = 0.02) and biceps skinfolds (6.03 ± 1.9 vs. 5.6 ± 1.7 mm; P = 0.04). Total fat mass and percentage body fat assessed by bioimpedance (n = 221) and DEXA (n = 114) were not different.CONCLUSIONSChildren exposed to metformin had larger measures of subcutaneous fat, but overall body fat was the same as in children whose mothers were treated with insulin alone. Further follow-up is required to examine whether these findings persist into later life and whether children exposed to metformin will develop less visceral fat and be more insulin sensitive. If so, this would have significant implications for the current pandemic of diabetes.

Background Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking. Methods We randomly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin (with supplemental insulin if required) or insulin. The primary outcome was a composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity. The trial was designed to rule out a 33% increase (from 30% to 40%) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin. Secondary outcomes included neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment. Results Of the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 0.99; 95% confidence interval, 0.80 to 1.23). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin. Conclusions In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment.

OBJECTIVEPregnant women with undiagnosed diabetes are a high-risk group that may benefit from early intervention. Extrapolating from nonpregnancy data, HbA 1c ‡6.5% (48 mmol/mol) is recommended to define diabetes in pregnancy. Our aims were to determine the optimal HbA 1c threshold for detecting diabetes in early pregnancy as defined by an early oral glucose tolerance test (OGTT) at <20 weeks' gestation and to examine pregnancy outcomes relating to this threshold. RESEARCH DESIGN AND METHODSDuring 2008-2010 in Christchurch, New Zealand, women were offered an HbA 1c measurement with their first antenatal bloods. Pregnancy outcome data were collected. A subset completed an early OGTT, and HbA 1c performance was assessed using World Health Organization criteria. RESULTSHbA 1c was measured at a median 47 days' gestation in 16,122 women. Of those invited, 974/4,201 (23%) undertook an early OGTT. In this subset, HbA 1c ‡5.9% (41 mmol/mol) captured all 15 cases of diabetes, 7 with HbA 1c <6.5% (<48 mmol/mol). This HbA 1c threshold was also 98.4% (95% CI 97-99.9%) specific for gestational diabetes mellitus (GDM) before 20 weeks (positive predictive value = 52.9%). In the total cohort, excluding women referred for GDM management, women with HbA 1c of 5.9-6.4% (41-46 mmol/mol; n = 200) had poorer pregnancy outcomes than those with HbA 1c <5.9% (<41 mmol/mol; n = 8,174): relative risk (95% CI) of major congenital anomaly was 2.67 (1.28-5.53), preeclampsia was 2.42 (1.34-4.38), shoulder dystocia was 2.47 (1.05-5.85), and perinatal death was 3.96 (1.54-10.16). CONCLUSIONSHbA 1c measurements were readily performed in contrast to the low uptake of early OGTTs. HbA 1c ‡5.9% ( ‡41 mmol/mol) identified all women with diabetes and a group at significantly increased risk of adverse pregnancy outcomes.

ObjectiveTo compare body composition and metabolic outcomes at 7–9 years in offspring of women with gestational diabetes (GDM) randomized to metformin (±insulin) or insulin treatment during pregnancy.Research design and methodsChildren were assessed at 7 years in Adelaide (n=109/181) and 9 years in Auckland (n=99/396) by anthropometry, bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) (n=92/99) and fasting bloods (n=82/99).ResultsIn the Adelaide subgroup, mothers were similar at enrollment. Women randomized to metformin versus insulin had higher treatment glycemia (p=0.002) and more infants with birth weight >90th percentile (20.7% vs 5.9%; p=0.029). At 7 years, there were no differences in offspring measures. In Auckland, at enrollment, women randomized to metformin had a higher body mass index (BMI) (p=0.08) but gained less weight during treatment (p=0.07). Offspring birth measures were similar. At 9 years, metformin offspring were larger by measures of weight, arm and waist circumferences, waist:height (p<0.05); BMI, triceps skinfold (p=0.05); DXA fat mass and lean mass (p=0.07); MRI abdominal fat volume (p=0.051). Body fat percent was similar between treatment groups by DXA and BIA. Abdominal fat percentages (visceral adipose tissue, subcutaneous adipose tissue and liver) were similar by MRI. Fasting glucose, triglyceride, insulin, insulin resistance, glycosylated hemoglobin (HbA1c), cholesterol, liver transaminases, leptin and adiponectin were similar.ConclusionsMetformin or insulin for GDM was associated with similar offspring total and abdominal body fat percent and metabolic measures at 7–9 years. Metformin-exposed children were larger at 9 years. Metformin may interact with fetal environmental factors to influence offspring outcomes.

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Background Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking. Methods We randomly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin (with supplemental insulin if required) or insulin. The primary outcome was a composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity. The trial was designed to rule out a 33% increase (from 30% to 40%) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin. Secondary outcomes included neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment. Results Of the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 0.99; 95% confidence interval, 0.80 to 1.23). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin. Conclusions In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment.

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