麻豆传媒

HAMBURG, Germany -- Faster-acting insulin aspart was safe for pregnant women with type 1 or 2 diabetes and resulted in fewer events of hypoglycemia, the randomized CopenFast trial found.

The mean infant birthweight standard deviation (SD) score was 1.0 in the faster-acting insulin aspart group versus 1.2 in the regular insulin aspart group (P=0.23), reported Lene Ringholm, PhD, of the Center for Pregnant Women with Diabetes at the University of Copenhagen in Denmark, during the European Association for the Study of Diabetes annual meeting.

On top of meeting the primary endpoint, women using faster-acting insulin aspart were less likely to have mild hypoglycemia at week 33 of pregnancy compared with those using regular insulin aspart (number of weekly mild events -0.90, 95% CI -1.71 to -0.09, P=0.030), the researchers pointed out in , where the study was simultaneously published.

"Our results show that there is a benefit, particularly regarding the women who have problems with hypoglycemia unawareness and a history of severe hypoglycemia because we just don't see so much severe hypoglycemia with the faster aspart," Ringholm said, adding that women who are planning to become pregnant should consider making the switch. "It's typically optimal to change medication before pregnancy, more so when it comes to insulin."

She suggested that clinicians should have this discussion with their patients during the pre-pregnancy planning process.

In an , Denice Feig, MD, MSc, of the University of Toronto in Canada, said that the inclusion of women with type 2 diabetes "may have diluted the findings," since women with type 1 diabetes are more likely to have poor glycemic control, glycemic variability, and greater risk for hypoglycemia and adverse pregnancy outcomes.

"The safety data should be reassuring to clinicians considering the use of faster aspart during pregnancy and adds to the several trials to date looking at other insulin analogues in pregnancy with reassuring results," Feig wrote.

In the current study, only one patient using faster-acting insulin aspart experienced a severe hypoglycemic episode, but there were 10 events in the conventional insulin aspart group (estimated treatment difference -0.08, 95% CI -0.16 to -0.01, P=0.026). The number needed to treat with faster insulin aspart to prevent one case of severe hypoglycemia was 18.

Overall, there were no significant differences in the number of adverse events or serious adverse events between the groups. None of the patients experienced diabetic ketoacidosis.

Ringholm explained that fetal overgrowth is common in pregnant women with either type of diabetes, though more common in type 1. However, severe hypoglycemia is a major concern during pregnancy, often hindering strict glycemic control.

"Faster-acting insulin aspart ... is an improved formulation of conventional aspart," she noted. In non-pregnant patients, it's been shown to improve HbA1c without increasing hypoglycemia and reduce postprandial glucose excursions.

In a subanalysis of women with type 1 diabetes using an intermittently scanned continuous glucose monitor, mean glucose levels were lower in those using faster insulin aspart at all timepoints throughout gestation. Patients on faster insulin apart also spent longer time within target range (63-140 mg/dL). "Women randomized to faster aspart obtained at least 70% time-in-range from 22 weeks onwards, while this was not obtained until 30 weeks in the women randomized to conventional aspart," said Ringholm.

The faster insulin aspart group also spent less time above target range. From 24 weeks onwards, these patients spent less than 25% of time above range, which wasn't achieved by conventional aspart users until week 32. However, there were no differences between the groups in regards to time spent below target range.

None of the laundry-list of secondary outcomes favored either treatment. One of these endpoints was average HbA1c at 33 weeks' gestation, which was 6.0% and 6.1% for the faster-acting and regular insulin aspart groups, respectively.

"We found that HbA1c declined from randomization until 21 weeks and remained stable thereafter with no differences between the two groups," said Ringholm. This was also the case for total insulin dose, which increased until around week 33 and then stabilized. This pattern was seen for both meal-time insulin and basal insulin doses in women using multiple daily injections or insulin pumps.

Large-for-gestational-age rates were still over 40% for both groups (41% for faster insulin aspart and 46% for regular insulin aspart), despite women achieving better glucose control throughout pregnancy, pointed out Fidelma Dunne, PhD, of the University of Galway in Ireland, who moderated the session.

"I think that our data suggest that we need to be really, really, really ambitious with our glycemic targets in this population," Ringholm responded. "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, so I think we 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."

Outcomes were also similar between groups at 3 months post-delivery -- the last check-in point of the trial.

This open-label study was conducted at Rigshospitalet in Copenhagen from November 2019 to May 2022, and randomized 203 pregnant women (average age 32) 1:1 to the two groups between weeks 8 and 13 of gestation; 72% had type 1 diabetes and 28% had type 2 diabetes. Most were on multiple daily injections at baseline, with an average daily insulin dose of 37 IU.