Historically, insulin has been considered standard therapy in women with gestational diabetes when target glucose levels cannot be consistently achieved through nutrition and exercise. It does not cross the placenta, and tight glycemic control can typically be achieved. Insulin therapy is typically added if fasting levels persistently exceed 95 mg/ dL in women with gestational diabetes. The American College of Obstetricians and Gynecologists (2017 a) also recommends that insulin be considered in women with I-hour postprandial levels that persistently exceed 140 mg/dL or those with 2-hour levelsr> 120 mg/dL. Importantly, all of these thresholds are extrapolated from recommendations for managing women with overt diabetes.
If insulin is initiated, the starting dose is typically 0.7 to 1.0 units/kg/d and is given in divided doses (American College of Obstetricians and Gynecologists, 2017a). A combination of intermediate-acting and short -acting insulin may be used, and dose adjustments are based on glucose levels at particular times of the day. At Parkland Hospital, the starting daily dose is divided so that two thirds is given in the morning before breakfast and one third in the evening before dinner. In the morning dose, one third is regular insulin and two thirds are NPH (neutral protamine Hagedorn). For the evening dose, one half is regular insulin and the other half is NPH. Insulin instruction for these women is accomplished either in a specialized outpatient clinic or during a short hospital stay. As shown in Table 57-8, insulin analogues such as insulin aspart and insulin lispro have a more rapid onset of action than regular insulin and theoretically could be helpful in postprandial glucose management. Experience with these analogues with gestational diabetes is limited, and Singh and coworkers (2009) were unable to demonstrate a beneit compared with conventional insulins.
Insulin is the preferred first-line agent for persistent hyperglycemia in women with gestational diabetes. However, both the American College of Obstetricians and Gynecologists (2017 a) and the ADA (20 17b) acknowledge that several studies support the safety and eicacy of either glyburide (Micronase) or metformin (Glucophage) (Langer, 2000; Nicholson, 2009; Rowan, 2008). Balsells and colleagues (2015) performed metaanalyses of trials comparing both agents to insulin or to each other. In the seven trials comparing glyburide with insulin, glyburide was associated with higher birthweight, more macrosomia, and more frequent neonatal hypoglycemia. In the six trials comparing metformin with insulin, metformin was associated with less maternal weight gain, more ?reterm birth, and less severe neonatal hypoglycemia. On average from all trials, treatment failures occurred in 6 percent of women treated with glyburide and 34 percent of those treated with metformin. In the two studies comparing oral hypoglycemic agents with each other, metformin treatment was associated with less maternal weight gain, lower birthweight, and less macrosomia. In contrast to trials of each agent compared with insulin, treatment failure rates of both agents in these two studies were equivalent. Importantly, in a randomized trial of glyburide treatment as an adjunct to diet therapy in 395 women with mild gestational diabetes, improvements in pregnancy outcomes in women treated with glyburide.