For women with gestational diabetes who cannot be treated with lifestyle intervention alone, the medical treatment of choice has for many years been insulin. The last decade or so, however, the use of oral hypoglycemic agents (OHA’s) has increased, also in Norway. The national guidelines in Norway state that insulin should be the main medical treatment. The increasing use of metformin is merely mentioned in these guidelines, but for whom or in which situations metformin may be applied, is not discussed.
We have therefore chosen to look into the following issue:Are oral hypoglycemic agents an alternative to insulin in the treatment of gestational diabetes?
Several studies have been performed regarding this issue, and the results overall point in the same direction; there is no conclusive evidence that oral hypoglycemic agents cause more adverse maternal or neonatal outcomes than insulin. In terms of hypoglycemic control, the failure rate (defined as not achieving glycemic control on maximum dosage) of glibenclamide was found to be only 4% in one large study (n=404), and varying from 16-21% in smaller studies. Metformin was found to have a failure rate of 46,3% in the largest RCT. Higher BMI, severe hyperglycemia and early diagnosis were found in the women in whom OHA’s failed to achieve glycemic control, suggesting pre-existing insulin resistance. There was no higher rate of adverse outcomes in this group compared to the groups that achieved glycemic control on either insulin or OHA’s alone.
In the case of glibenclamide, no large RCT has been published since 2000. Al though the more recent randomized studies have corroborated findings from 2000, a cohort from 2012 found an increased risk of macrosomia and admission to the ICU in the glibenclamide group. There is therefore a need for a large, randomized study before drawing any conclusions.
In the case of metformin, the large MiG-trial (n=733) was published in 2008. Both this and a two-year-follow-up study show promising results. As long as metformin is used for treating women with mild or moderate gestational diabetes, we see no contraindications, given a close follow-up of the glycemic control.