Proven Efficacy and Safety of Insulin Degludec in the Treatment of Type 1 Diabetes in Pregnant Women

Abstract

Diabetes mellitus (DM) remains a disease that determines the high frequency of obstetric and perinatal complications. Achieving the physiological values of glycemia as the main condition for the successful course and outcomes of pregnancy in women with diabetes remains a difficult task to date. To improve the quality of treatment of patients with DM 1 type, the method of basic bolus insulin therapy has been used for more than 30 years. Therefore, the emergence of new effective and safe insulins is extremely important for improving pregnancy outcomes in patients with diabetes. Insulin degludec is an analogue of basal insulin of the new generation with improved pharmacokinetic and pharmacodynamics profiles compared to analogues of basal insulins of the previous generation, however, there was insufficient data on its use during pregnancy. This article presents the results of an open international randomized controlled study of EXPECT no less effective use of insulin degludec during pregnancy, which took place in 14 countries in 56 research centers, 8 of them in Russia. Of the 225 women with DM 1 type who participated in the study, 67 were from Russia. The EXPECT study compared the efficacy and safety of insulin degludec with insulin detemir (both in combination with insulin aspart) in pregnant women with DM 1 type. Insulin detemir was chosen as a comparison drug, since it is the first basal insulin analog approved for use during pregnancy and most often recommended as a first-line drug when choosing long-acting insulin for the treatment of diabetes in pregnant women. Material and methods. The study included women over the age of 18 with DM 1 type, whose gestation period ranged from 8 (+0 days) to 13 (+6 days) weeks and who were just planning a pregnancy. The study participants (1:1) were randomized using an interactive Internet system for the use of insulin degludec at a dose of 100 U/ml once a day or insulin detemir at a dose of 100 U/ml once or twice a day, while both drugs were taken in combination with insulin aspart at a dose of 100 U/ml. Pregnant women received the study drug at randomization, throughout the entire period of pregnancy and up to 28 days after delivery (the end of the study). Women who were not pregnant at the time of randomization started taking the study drug before conception. The primary endpoint is the last scheduled measurement of glycated hemoglobin (HbA1c) before childbirth (a field of at least 0.4% efficiency for degludec compared to detemir). Secondary endpoints are efficacy, safety for the mother, and pregnancy outcomes. The primary endpoint was evaluated in all randomized women who were pregnant during the study. Safety – for all participants who were pregnant during the study and received at least one dose of the study drug. This study is registered on the website ClinicalTrials.gov numbered NCT03377699 and currently completed. Results. From November 22, 2017 to November 8, 2019, out of 296 screened women, 225 were randomized for insulin degludec (n = 111) or insulin detemir (n = 114). The average HbA1c value at the initial stage of pregnancy in the degludec insulin group was 6.6% with a standard deviation (SD) of 0.6%, in the detemir insulin group -6.5% with SD of 0.8%. In the degludec insulin group, the average value of the last planned measurement of HbA1c before childbirth was 6.2% (SD – 0.07%; 45 mmol/mol), in the detemir insulin group – 6.3% (SD – 0.07%; 46 mmol/mol). The estimated difference between the treatment groups is -0.11% (95% CI -0.31–0.08); -1.2 mmol/mol (95% CI -3.4–0.9); p < 0.0001 which confirms the equally effective effectiveness of insulin degludec. When using insulin degludec, no additional safety-related problems were reported compared to the use of insulin detemir.