Principal Epidemiologist Novo Nordisk A/S Søborg, Denmark
Background: Although randomized trials have provided reassuring evidence for the safety and effectiveness of insulin analogues during pregnancy for women with diabetes, there is a scarcity of real-world evidence on the safety and effectiveness of insulin aspart (IAsp) for the treatment of pregnant women with pre-existing type 1 diabetes (T1D).
Objectives: This post hoc analysis of the real-world EVOLVE study investigated safety and effectiveness of IAsp versus other bolus insulins in pregnant women with pre-existing type 1 diabetes.
Methods: EVOLVE is a prospective non-interventional study designed to investigate the safety and effectiveness of insulin detemir versus other basal insulins during pregnancy for women with pre-existing diabetes. Many women in the study were also using bolus insulins, which allowed this post-hoc analysis, comparing IAsp to other bolus insulins in pregnant women with pre-existing T1D. The participants included in the present analysis were pregnant women who did not change bolus insulin (or basal insulin if used) in the four weeks prior to conception and during pregnancy. Exclusion criteria included multiple pregnancy, and treatment with oral antidiabetic medications, biphasic insulin or a glucagon-like peptide-1 receptor agonist. Maternal and pregnancy outcomes were assessed by estimating risk differences with and without adjustment for potential confounders using propensity score matching. The primary endpoint was the risk of major congenital malformations, neonatal or perinatal death. A comparison of the glycaemic control between the two treatment groups was also conducted using mixed models for repeated measurements with and without adjustment for potential confounders.
Results: In total, 1434 women were treated with IAsp and 406 with other bolus insulins at enrolment. Following propensity score matching, the two treatment groups were balanced, and each group included 381 women. No significant differences were seen with IAsp versus other bolus insulins in the risk of different maternal and pregnancy endpoints including the risk of major congenital malformations, neonatal or perinatal death, major maternal hypoglycemia, abortion, pre-term delivery, pre-eclampsia, birthweight large for gestational age, major congenital malformations, perinatal death and neonatal death, in the crude and adjusted analyses (p values > 0.05). Nonetheless, a significantly lower mean A1c value in the third trimester was observed with IAsp compared to other bolus insulins (adjusted % point difference –0.16% [95% CI –0.28; –0.05]; p=0.005).
Conclusions: Compared with other bolus insulins, IAsp was associated with significantly lower A1c during the third trimester and a similar risk of adverse pregnancy outcomes.
