Optimal Management of Gestational Diabetes Mellitus
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.
Source Elsevier Global Medical News
GDM and the Developing Fetus
A growing body of research has convincingly demonstrated that even periods of mild hyperglycemia during pregnancy can have long-term adverse consequences on the developing fetus. Therefore, there is a growing sentiment in the ob.gyn. and diabetes communities for an aggressive approach to the detection, treatment, and monitoring of the most frequent causes of hyperglycemic events during pregnancy. Significant controversies remain on how best to implement this approach.
In the area of gestational diabetes mellitus (GDM) treatment, multiple controversies exist regarding whether to manage GDM very aggressively (i.e., with insulin as the first line of therapy) or with less aggressive approaches first, followed by insulin as a last resort. The former approach, while likely to be effective in controlling hyperglycemia, is viewed by many physicians – and their patients – as not acceptable given that GDM is a relatively mild form of diabetes and most cases will resolve spontaneously after pregnancy.
In this month's Master Class, Dr. Thomas R. Moore, professor and chairman of the department of reproductive medicine at the University of California, San Diego, returns to provide us with a superbly written essay on the state of the evidence in managing GDM. Dr. Moore's Master Class briefly discusses the growing prevalence of GDM in the United States and worldwide, as well as the scientific evidence linking intrauterine hyperglycemia with adverse pregnancy outcomes. He then provides a detailed analysis of the best available science on trials of dietary approaches to GDM as well as trials on oral antihyperglycemic drugs and how they compare with one another and with insulin.
Dr. Moore also demonstrates how this knowledge is being applied to his own patients as well as how they've been able to adapt, accept, and comply with this relatively new approach to managing GDM. Once again, we are honored that Dr. Moore has agreed serve as the Master Class guest professor, providing important insights into how GDM might be managed optimally.
Key Points
▸ Prenatal exposure to hyperglycemia programs the fetus for a higher risk of being born overweight, of becoming obese in adolescence or adulthood, and of developing diabetes later in life. Two randomized trials have demonstrated the positive impact of treating even mild forms of GDM.
▸ Many patients can be managed with diet alone, but the effectiveness of dietary treatment must be carefully monitored, with insulin or oral antihyperglycemic agents added early – before significant body fat is accumulated by the fetus.
▸ Glyburide is just as effective as insulin in achieving optimal glycemic control and is significantly less likely to cause hypoglycemia in mothers, with no adverse neonatal or fetal effects, numerous studies have shown. Glyburide is not a 12-hour medication in pregnant women as it is in nonpregnant women, however. Ob.gyns must appreciate the dosing implications of the agent's different pharmacodynamics in pregnancy.
