Safety considerations with pharmacological treatment of gestational diabetes mellitus

The number of women with gestational diabetes mellitus (GDM: diabetes first diagnosed in pregnancy) continues to grow, as do the associated risks of antenatal and postnatal complications and the chance of future diabetes and obesity in both mother and offspring. Recent randomised controlled trials have demonstrated clear benefits for intensive management of GDM using lifestyle modification, self blood glucose monitoring, close clinical supervision and, where glycaemia remains inadequately controlled, insulin therapy. More recently, metformin and glibenclamide have been shown to adequately reduce hyperglycaemia as part of a stepped approach to GDM management, with a switch to insulin therapy where necessary. Other oral medications have not been shown to be safe in pregnancy. Human insulin therapy is safe within the limits of hypoglycaemia and weight gain. Most insulin analogues are also now considered safe for use in pregnancy (insulin lispro, aspart and detemir). Metformin therapy is oral, and therefore preferred to insulin, but is associated with more gastrointestinal adverse effects, although not hypoglycaemia or weight gain. Conversely, glibenclamide is also an oral therapy but is associated with hypoglycaemia and weight gain. However, metformin crosses the placenta and it remains unclear whether glibenclamide crosses the placenta or not: long-term risks have not been shown, and are thought to be minimal, but further studies are needed. Metformin is seen by some as the treatment of choice where weight gain is an issue, providing that the unanswered questions over the long-term safety of oral agents have been discussed.