Faster-acting insulin aspart may be safely used in expectant mums with diabetes

Treatment with faster-acting insulin aspart in pregnant women with diabetes appears to have no adverse effect on foetal growth and even leads to fewer episodes of hypoglycaemia, according to the Copenfast trial.

Data from a cohort of 203 pregnant women with type 1 or 2 diabetes showed that birthweight SD score was comparable in the faster-acting insulin aspart (n=101) and the conventional insulin aspart (n=102) arms (mean 1.0 vs 1.2; estimated treatment difference, –0.22, –0.58 to 0.14; p=0.23), reported senior study author Assoc Prof Lene Ringholm of the Center for Pregnant Women with Diabetes at the University of Copenhagen, Copenhagen, Denmark. [Nørgaard S, et al, EASD 2023]

The same was true for other pregnancy outcomes, with no significant between-group difference seen in large for gestational age (LGA; 41 percent vs 46 percent; p=0.39), small for gestational age (3 percent vs 2 percent; p=0.64), pre-eclampsia (14 percent vs 10 percent; p=0.36), preterm delivery (<37 weeks; 19 percent vs 22 percent; p=0.64), and gestational weight gain (13.7 vs 13.4 kg; p=0.83).

Furthermore, women who received faster-acting vs conventional insulin aspart had a lower incidence of mild hypoglycaemia (symptoms that were self-manageable) at week 33 of pregnancy (p=0.03), as well as severe hypoglycaemia during pregnancy (one vs 10 events; p=0.03). The number needed to treat with faster-acting insulin aspart to prevent one episode of severe hypoglycaemia was 18.

“Faster-acting insulin aspart is an improved formulation of the conventional [drug]. Outside of pregnancy, the faster-acting [formulation] reduces postprandial glucose excursions and improves HbA1C without increasing hypoglycaemia,” Ringholm noted.

“Our results show that there is a benefit [for pregnant] women who have problems with hypoglycaemia and a history of having severe hypoglycaemia,” having seen infrequent severe hypoglycaemic events with faster-acting insulin aspart, she added.

Study details

Copenfast was an open-label, randomized controlled trial that included pregnant women with diabetes, including those with type 1 diabetes on multiple daily injections, type 1 diabetes on insulin pump, and type 2 diabetes requiring insulin. These women were randomly assigned to receive faster-acting or conventional insulin aspart between 8 and 14 weeks of pregnancy. Everyone was followed until 3 months postdelivery.

“We found that HbA1c declined from randomization until 21 weeks and remained stable thereafter, with no differences between the two groups,” Ringholm said.  

Likewise, total insulin dose used during pregnancy increased from baseline to week 33 and then stabilized through week 35. This pattern was observed for both meal-time insulin and basal insulin doses in women using multiple daily injections or insulin pumps.

Ringholm noted that based on the 7-day data on 7-point blood glucose profiles of the participants, level 2 hypoglycaemia (blood glucose <3.0 mmol/L) occurred rarely throughout pregnancy, with no difference between the two groups.

These data suggest that “faster-acting insulin aspart can be used in women with type 1 or type 2 diabetes during pregnancy and postdelivery with no additional safety issues,” she said.

Ambitious glycaemic targets

In a question-and-answer session, when asked whether women on insulin who are planning pregnancy can be switched to the faster-acting formulation even before conception, Ringholm stated that switching medications before pregnancy is ideal.

Subsequently, one of the study moderators, Dr Fidelma Dunne of the University of Galway, Galway, Ireland, pointed out the relatively high incidence of LGA births despite glucose control throughout pregnancy. Dunne asked Ringholm whether there might be something that needed to be targeted to minimize such outcome.

“I think that our data suggest that we need to be really, really, really ambitious with our glycaemic targets in this population, because we obtained near-normal HbA1c levels, but still we did not obtain the target. And we did not obtain time-in-range in our women with type 1 diabetes until after 20 weeks,” Ringholm responded.

“[W]e need to go home and work even harder to obtain time-in-range early in pregnancy because there seems to be a lot going on, particularly in the very first few weeks of pregnancy,” she added.