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

Background: Gestational diabetes mellitus (GDM) 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 existing management strategies. Ursodeoxycholic acid (UDCA) is commonly used for cholestasis in pregnancy and has shown potential metabolic benefits, including improved insulin sensitivity and reduced inflammation. We hypothesize that UDCA may improve glycemic control in GDM.

Objective: to compare treatment with ursodeoxycholic acid (UDCA) versus placebo to improve maternal glycemia in GDM.

Study design: single-site, randomized, double-blinded, placebo-controlled trial of UDCA in 113 women with GDM at 24-28 weeks' gestation. The primary outcome was maternal fasting blood glucose concentration at 35⁺⁰-37⁺⁶ weeks' gestation.

Results: The primary outcome did not differ significantly between groups when evaluated by intention to treat (treatment effect 0.98 (95% CI 0.92 to 1.05, p=0.61)); 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 pre-specified secondary analysis measured serum concentrations of UDCA using UPLC-MS/MS and showed that participants taking larger numbers of tablets had higher serum concentrations of UDCA. Post hoc analysis revealed no difference in the rate of fasting blood glucose concentrations at or above the recommended target of 90mg/dL according to intention to treat (5/50 (10.0%) versus 8/53 (15.1%), RR 0.66, 95% CI 0.23 to 1.89, p=0.557). However, in patients with serum UDCA ≥0.5µmol/L, consistent with having taken UDCA, fewer patients had fasting glucose above target (2/42 (4.8%) versus 11/57 (19.3%), RR 0.25, 95% CI 0.06 to 1.06, p=0.039).

Conclusions: This trial demonstrated no difference in fasting glycemia for women with GDM treated with UDCA compared to placebo. However, those with elevated serum UDCA concentrations were more likely to have fasting blood glucose concentrations below recommended thresholds, suggesting potential benefit of further investigation.