Metformin also has a theoretical advantage over glyburide since its mechanism of action gets directly to the root of the problem of GDM. Metformin is an insulin sensitizer, and the root cause of GDM is resistance to insulin, or insulin insensitivity, at the tissue level.
In a study by Dr. J.A. Rowan published in 2008 that randomized more than 700 patients to either insulin or metformin, there were no appreciable differences in neonatal and maternal outcomes – from birth weight and neonatal morbidity to maternal hypoglycemia and glycemic control (N. Engl J. Med. 2008;358:2003-15). However, whereas 4% of the glyburide group in Dr. Langer’s trial had to eventually add insulin (and up to 10%-20% in other studies), 47% of the patients taking metformin in this trial had to add insulin to maintain glycemic control.
Indeed, the downside to metformin, this and other studies have shown, is a high so-called failure rate – the need for supplementary insulin, which in this case typically occurs later in the pregnancy – of between 30% and 50%.
On the other hand, patients generally will be more satisfied starting treatment with metformin than insulin. In weighing glyburide and metformin, patients should be counseled about their chances of needing insulin later in the pregnancy: about 10% with glyburide and closer to 50% with metformin.
In terms of glycemic control and other outcomes, several smaller, recent studies comparing the two agents have shown no statistical difference between them. Interestingly, most studies have shown less maternal weight gain in patients taking metformin than glyburide – about 6 pounds – but the significance of this difference is unclear since the babies’ birth weights were not appreciably different.
Dr. Moore said he had no relevant financial disclosures.