Glibenclamide treatment in gestational diabetes linked to morbidities in newborns

Babies whose mothers have used glibenclamide for treating gestational diabetes are at an increased risk of intensive care unit admission, a study suggests.

Treatment with glibenclamide is associated with an increased risk of adverse events for newborns compared to those whose mothers used insulin, study finds

Treatment with glibenclamide is associated with an increased risk of adverse events for newborns compared with those whose mothers used insulin, a study published in JAMA Pediatrics
on 30 March 2015 shows.

Looking at ten years of US data, researchers identified 9,173 pregnant women with gestational diabetes who had been treated with glibenclamide (glyburide in the United States) or insulin within 150 days of delivering their babies. Around 54% of women were treated with glibenclamide (4,982 women) and 45.7% (4,191) with insulin.

The researchers found a higher risk of neonatal intensive care unit admission (relative risk [RR] 1.41; 95% confidence interval [CI], 1.23–1.62), respiratory distress (RR 1.63; 95% CI, 1.23–2.15), neonatal hypoglycaemia (RR 1.40; 95% CI, 1.00–1.95), birth injury (RR 1.35; 95% CI 1.00–1.82) and “large for gestational age” (RR 1.43; 95% CI 1.16–1.76) among newborns whose mothers were given glibenclamide, compared with those who had been given insulin.

Lead researcher Michele Jonsson-Funk, from the University of North Carolina at Chapel Hill, says further research is needed to assess the long-term effects of glibenclamide on infants.

Richard Holt, a professor of medicines at the University of Southampton, writes in an editorial[2]
accompanying the study that it “heightens residual concerns” about the use of glibenclamide in gestational diabetes. He points out that the researchers had omitted socio-demographic details about the women – such as their race, education and body weight – which could influence the outcome of a pregnancy.

Jonsson-Funk countered that the researchers were looking at other data sources, such as birth registries, administrative databases from public and private insurers or electronic health records to try to address these omissions.

Glibenclamide has become a popular choice among physicians, according to Jonsson-Funk, since a trial[3]
was published in 2000 considering its equivalence to insulin in treating gestational diabetes.

Its main appeal is its delivery as a pill versus the injectable insulin for pregnant women, but researchers have begun to question its safety for newborns, suggesting that it does cross the placenta to affect the foetus.

Rosa Corcoy, assistant professor in endocrinology and nutrition at the Santa Creu and Sant Pau Hospital, Barcelona, Spain, thinks that an alternative antidiabetes drug, metformin, should be used instead of glibenclamide. But knowledge about metformin’s ability to cross the placenta is also limited, adds Corcoy.

Jonsson-Funk and colleagues found no association between the use of glibenclamide and pregnancy-associated complications like obstetric trauma, preterm birth or infant jaundice. Jonsson-Funk thinks the study should not necessarily create fears over the drug, or that it should be abandoned for treatment, but urges physicians to be vigilant when identifying women for glibenclamide treatment.

In the UK, the National Institute for Health and Care Excellence recommends that doctors consider using glibenclamide for women with gestational diabetes in whom blood glucose targets are not achieved with metformin but who refuse insulin or for women who cannot tolerate metformin.

  • This story was amended on 9 April 2015 to clarify a comment from the lead researcher.


[1] Castillo WC, Boggess K, Stürmer T et al. Association of adverse pregnancy outcomes with glyburide vs insulin in women with gestational diabetes. JAMA Pediatrics 2015;169(5). doi:10.1001/jamapediatrics.2015.74.

[2] Holt RIG. Glyburide for Gestational Diabetes: Time for a Pause for Thought. JAMA Pediatrics 2015;169(5). doi:10.1001/jamapediatrics.2015.144.

[3] Langer O, Conway DL, Berkus MD et al. A comparison of glyburide and insulin in women with gestational diabetes mellitus. The New England Journal of Medicine 2000;343:1134–1138. doi:10.1056/NEJM200010193431601.

Last updated
The Pharmaceutical Journal, PJ, 18 April 2015, Vol 294, No 7858;294(7858):DOI:10.1211/PJ.2015.20068281

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