Detemir versus Neutral Protamine Hagedorn Insulin for Diabetes Mellitus in Pregnancy: A Comparative-Effectiveness, Randomized Controlled Trial.

Abstract Background Insulin detemir, being used increasingly during pregnancy, may have pharmacological benefits compared to neutral protamine Hagedorn (NPH). Objective We evaluated the probability that treatment with insulin detemir compared to NPH reduces the risk for adverse neonatal outcome among individuals with Type 2 diabetes mellitus or overt type 2 (gestational diabetes diagnosis Study design We performed a multiclinic randomized controlled trial (09/2018 to 01/2020), which included singleton gestation with Type 2 diabetes or overt type 2 who sought obstetrical care ≤21 weeks. Participants were randomized to receive either insulin detemir or NPH by a clinic-stratified scheme. Primary outcome was a composite of adverse neonatal outcomes including; shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need for at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. Secondary neonatal outcomes included gestational age at delivery, small for gestational, 5-minute Apgar score 75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50-50 likelihood of either intervention being better; NCT 03620890). Results There were 108 people randomized in this trial (57 insulin detemir; 51 NPH), and 103 were available for analysis of the primary outcome (N=5 for pregnancy loss before 24 wks). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir relative to NPH (posterior adjusted relative risk, 0.88, 95% credible interval, 0.61 – 1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with use of insulin detemir vs NPH, e.g. maternal hypoglycemic events (97% probability of benefit, posterior adjusted relative risk 0.59, 95% credible interval, 0.29 – 1.08), and hypertensive disorders (88% probability of benefit, posterior adjusted relative risk 0.81, 95% credible interval 0.54 – 1.16) Conclusion In our comparative effectiveness trial involving individuals with type 2 diabetes or overt type 2, use of insulin detemir compared to NPH resulted in lower rates of adverse neonatal and maternal outcomes.