Glyburide ‘not justified’ as first-line gestational diabetes treatment
medwireNews: A head-to-head trial in women with gestational diabetes has failed to prove that glyburide is statistically noninferior to insulin in terms of perinatal outcomes.
The findings published in JAMA show that perinatal complications associated with gestational diabetes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia) occurred at a rate of 27.6% among women using glyburide and 23.4% among those using insulin. This gave a difference of 4.2%, but the upper limit of the confidence interval was 10.5%, which exceeded the prespecified margin for noninferiority of 7.0%.
In a linked editorial, Donald Coustan (Warren Alpert Medical School of Brown University, Jamestown, Rhode Island, USA) and Linda Barbour (University of Colorado School of Medicine, Aurora, USA) caution that “[f]ailure to demonstrate noninferiority does not mean that glyburide is inferior to insulin.”
However, they point out that the trial was designed to address the adverse effects of glyburide reported by previous, less rigorous studies, so in this context the “previously proposed disadvantages of glyburide have not been disproven.”
Marie-Victoire Sénat (Hôpital Bicêtre, Paris, France) and study co-authors randomly assigned 367 women with gestational diabetes to receive glyburide and 442 to take insulin. The women had fasting blood glucose of at least 95 mg/dL or 2-hour postprandial levels of at least 120 mg/dL, even after 10 days of following a dietician-prescribed diet.
The team notes that use of glyburide to treat gestational diabetes is relatively common in the USA, but not in Europe, despite the obvious advantages of an oral over an injectable treatment.
Women assigned to take glyburide started at a dose of 2.5 mg once daily, increasing to a maximum of 20 mg per day and then switching to insulin if glycemic control was still not achieved. Women started on rapid insulin analogs, which was dose-adjusted according to postprandial glucose levels, and added basal insulin if needed, adjusted according to morning fasting glucose.
Rates of secondary neonatal outcomes, including admission to neonatal intensive care unit, ponderal index, and respiratory distress syndrome, did not differ according to maternal diabetes treatment.
This, and the slightly poorer primary outcome among women taking glyburide, occurred despite glyburide delivering significantly better fasting glucose levels, with 71.7% of women maintaining levels below 95 mg/dL, compared with 63.2% of those using insulin. The corresponding rates of postprandial glucose control were 57.8% versus 49.3%, with this difference only just failing to achieve statistical significance (p=0.051). However, more women in the glyburide group had hypoglycemia or severe hypoglycemia.
In their editorial, Coustan and Barbour stress that the advantages of being able to take glyburide orally must be set against the possibly increased risk for perinatal complications and the lack of data on long-term safety.
“Use of glyburide may be most appropriate when insulin injections are not acceptable or practical,” they suggest.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group
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