Fetal overgrowth is associated with a lack of HbA1c control during pregnancy and is a common obstetric condition among women with type 1 (T1D) and type 2 (T2D) diabetes.1 Glycemic control is complicated among pregnant women with studies showing ≥45% of pregnant women with T1D experiencing ≥1 episode of severe hypoglycemia during pregnancy, particularly in the first trimester.1 To avoid hypoglycemia, it was suggested that continuous glucose monitoring, as well as the use of insulin analogs such as insulin aspart (IAsp) paired with an adequate reduction of insulin, may help reduce instances of hypoglycemia in this population.1 IAsp is widely used in the pregnant population. Its improved formulation, fast-acting insulin aspart (faster aspart), has shown robust efficacy in the reduction of postprandial glucose excursions as well as improvements in HbA1c without increasing hypoglycemia among non-pregnant populations.1 It is considered safe for pregnancy, however, its use in this population has yet to be thoroughly evaluated.1  

At the 2023 European Association for the Study of Diabetes (EASD) Annual Meeting, Dr. Lene Ringholm shared the results from the CopenFast trial which was a single-center, open-label trial designed to investigate the difference between faster aspart and IAsp in fetal growth and glycemic control during pregnancy and post-delivery in women with T1D or T2D between 2019 and 2022.1 Pregnant women with T1D or T2D were recruited and randomized to receive faster aspart (n=101) or IAsp (n=102) between weeks 8 to 14 and were followed up to 3 months after delivery. Randomization was stratified by diabetes type and treatment modality.1 

The primary endpoint of birthweight standard deviation (SD) score with faster aspart vs. IAsp (1.0±1.4 vs. 1.2±1.3) was not significantly different (p=0.23) and remained similar at 3 months postpartum (-0.5±1.9 vs. -0.3±1.6; p=0.39).1 No significant difference was reported for large gestational age infants at 41% vs. 46% (p=0.39).1 Rates of preeclampsia (14% vs. 10%; p=0.36) or preterm delivery defined as <37 gestational weeks (19% vs. 22%; p=0.64) were similar in both arms.1 

In terms of glycemic control, HbA1c stabilized at around 6%, starting at week 21 in both arms.1 The 7-point blood glucose profile over 7 days was comparable through week 33 as well.1 The total dose of insulin, including mealtime insulin or basal insulin regardless of treatment modality, gradually increased over time at a similar rate in both arms.1 In a subgroup of pregnant women with T1D who had intermittently scanned continuous glucose monitoring (isCGM) (n=111), 70% time in range (3.5-7.8 mmol/L) was achieved 8 weeks earlier at week 22 with faster aspart than with IAsp.1 The time below range (<3.5mmol/L) in this subgroup was around 5% throughout the pregnancy with both treatments.1 No significant difference in HbA1c (p=0.16) was reported at 3 months post-partum.1s 

In the safety analysis, the rates of adverse events (p=0.45) and serious adverse events (p=0.25) were similar.1 No adverse events that led to discontinuation and perinatal deaths were reported.1 During pregnancy, women using faster aspart reported significantly fewer incidences of mild hypoglycemia events (2.0 vs. 3.0 episodes per week; p=0.03) while the rate of moderate hypoglycemia was similar and stable in both arms.1 Fewer women had severe hypoglycemia in the faster aspart arm (1 vs. 7; p=0.06), culminating in significantly fewer severe hypoglycemic events (1 vs. 10; p=0.03). The number needed to treat (NNT) for the faster aspart arm was 18 to prevent 1 severe hypoglycemic event.1 No significant difference in the rates of severe hypoglycemia (p=0.65) was reported at 3 months post-partum.1 

Dr. Ringholm cautioned that any changes in medication should be done prior to the pregnancy, particularly among patients with hypoglycemia unawareness or severe hypoglycemia.1 It is also important to discuss with women during pregnancy planning about which modality of insulin to use.1 She also conceded that a lot of the women had suboptimal HbA1c levels, particularly before week 20, and that glycemic targets should be set more ambitiously in this population.1 Further research is required to better adjust diabetes treatment to early pregnancy.1