Randomized controlled trial of the impact of ursodeoxycholic acid on glycemia in gestational diabetes mellitus: the GUARDS trial

Abstract

BACKGROUND

Gestational diabetes mellitus is a pregnancy complication that can be associated with increased risks of adverse maternal and neonatal outcomes. Optimal glycemic control remains challenging for many patients despite the existing management strategies. Ursodeoxycholic acid is commonly used for cholestasis of pregnancy and has shown potential metabolic benefits, including improved insulin sensitivity and reduced inflammation. We hypothesize that ursodeoxycholic acid may improve glycemic control in gestational diabetes mellitus.

OBJECTIVE

This study aimed to compare treatment with ursodeoxycholic acid vs placebo for improving maternal glycemia in gestational diabetes mellitus.

STUDY DESIGN

This was a single-site, randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in 113 women with gestational diabetes mellitus at 24 to 28 weeks’ gestation. The primary outcome was maternal fasting blood glucose concentration at 35⁺⁰ to 37⁺⁶ weeks’ gestation.

RESULTS

The primary outcome did not differ significantly between groups when evaluated by intention to treat analysis (treatment effect, 0.98; 95% confidence interval, 0.92–1.05; P=.61). There were no differences in maternal or fetal secondary outcomes, including maternal weight change, need for insulin treatment, birthweight centile, proportion of large or small for gestational age infants, neonatal hypoglycemia, or admission to the neonatal unit. A prespecified secondary analysis measured serum concentrations of ursodeoxycholic acid using ultra-performance liquid chromatography–tandem mass spectrometry and showed that participants taking larger numbers of tablets had higher serum concentrations of ursodeoxycholic acid. Post hoc analysis revealed no difference in the rate of fasting blood glucose concentrations at or above the recommended target of 90 mg/dL according to intention to treat analysis (5/50 [10.0%] vs 8/53 [15.1%]; risk ratio, 0.66; 95% confidence interval, 0.23–1.89; P=.557). However, among patients with serum ursodeoxycholic acid ≥0.5 µmol/L (indicating adherence), fewer patients had fasting glucose levels above the target (2/42 [4.8%] vs 11/57 [19.3%]; risk ratio, 0.25; 95% confidence interval, 0.06–1.06; P=.039).

CONCLUSION

This trial demonstrated no difference in fasting glycemia between women with gestational diabetes mellitus treated with ursodeoxycholic acid and those treated with placebo. However, those with elevated serum ursodeoxycholic acid concentrations were more likely to have fasting blood glucose concentrations below the recommended thresholds, suggesting potential benefit of further investigation.