Aim: To evaluate the effect of faster-acting insulin aspart (faster aspart) vs. insulin aspart (IAsp) on fetal growth and glycemic control in pregnant women with type 1 or type 2 diabetes. Methods: In a single-center, open-label trial from November 2019 to May 2022 women were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump) and randomized to faster aspart or IAsp from 8 to 13 weeks. Primary outcome was offspring birthweight standard deviation (SD) score. Secondary outcomes included mild hypoglycemia (managed by the woman) in the previous week, HbA1c at inclusion, 21, 33, and 35 weeks, and severe hypoglycemia (requiring third party assistance) reported in a structured interview. Results: In total, 216 women were included and randomized to faster aspart or IAsp (n=109 vs. n=107). Baseline data were comparable in both groups. Primary outcome data were available in 94% (71% type 1 (of which 19% on insulin pump), 29% type 2 diabetes). Offspring birthweight SD score was median 0.7 (interquartile range -0.3-2.0) vs. 1.1 (0.4-1.9), mean difference -0.2 (95% confidence interval -0.6-0.1), p=0.23 with 41% vs. 46% large for gestational age infants (p=0.39). From randomization to delivery 1 (1%) vs. 7 (7%) women reported severe hypoglycemia (p=0.07) with fewer events reported by women using faster aspart compared to IAsp (1 vs. 10 events, p=0.03). At 33 weeks, women using faster aspart reported fewer mild hypoglycemic events in the previous week compared to IAsp (2.0 (0.8 - 4.0) vs. 3.0 (1.0 - 5.0), p=0.03), while HbA1c was 41 (38-46) vs. 43 (39-46) mmol/mol, p=0.28. Prevalence of preeclampsia was 15% vs. 12% (p=0.51) and preterm delivery <37 weeks 19% vs. 22% (p=0.64). No perinatal deaths were reported. Conclusion: In pregnant women with type 1 or type 2 diabetes, use of faster aspart resulted in comparable fetal growth and HbA1c with less severe hypoglycemia compared to IAsp. Disclosure S.K.Noergaard: Research Support; Novo Nordisk A/S. E.R.Mathiesen: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk, Research Support; Medtronic, Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Novo Nordisk, Stock/Shareholder; Novo Nordisk. T.D.Clausen: None. J.Søholm: Research Support; Novo Nordisk A/S. P.Holmager: None. N.C.Do: Research Support; Novo Nordisk Foundation. P.Damm: Other Relationship; Novo Nordisk A/S. L.Ringholm: Research Support; Novo Nordisk A/S. Funding Novo Nordisk A/S (U1111-1209-6358)

Aim: To evaluate the prevalence of preeclampsia before and after implementing a change from a risk-based aspirin prophylaxis to prophylactic aspirin to all pregnant women with pre-existing diabetes. Methods: A prospective cohort study of 410 consecutive pregnant women with pre-existing diabetes (257 with type 1 and 153 with type 2 diabetes); 203 women (selected-cohort) prior to February 2018 where aspirin was prescribed to selected women at risk of preeclampsia followed by 207 women (all-cohort) who all were prescribed aspirin according to the new aspirin prophylaxis strategy. The primary outcome was preeclampsia. Results: Documented prescription of aspirin at approximately 10 weeks increased from 25% (selected-cohort) to 88% (all-cohort). In the all-cohort vs. selected-cohort HbA1c (median 46 mmol/mol (interquartile range 42-53) vs. 47 (43-53), p=0.18), parity, chronic hypertension, home blood pressure, microalbuminuria/diabetic nephropathy and smoking were similar in early pregnancy. In the all-cohort fewer women had type 2 diabetes (32% vs. 42%, p=0.04) and BMI tended to be lower (p=0.05). The prevalence of preeclampsia was unchanged (12% vs.11%, p=0.69) in the all- vs. selected-cohort and similar results were seen when stratifying for diabetes type. Preterm delivery <37 weeks (23% vs. 27%, p=0.30), preterm delivery with preeclampsia (7% vs. 7%, p=0.96), and large and small for gestational age infants (40% vs. 32% (p=0.07) and 7% vs. 6% (p=0.88), respectively) were similar in the two cohorts. Conclusion: Implementation of prophylactic aspirin to all pregnant women with pre-existing diabetes was not followed by a decline in the prevalence of preeclampsia. The possible effect of aspirin prophylaxis in women with diabetes needs to be further evaluated in randomized controlled trials. Disclosure N. C. Do: None. M. Vestgaard: None. B. Ásbjörnsdóttir: Employee; Self; Novo Nordisk A/S. S. K. Noergaard: Research Support; Self; Novo Nordisk. L. Ringholm: Research Support; Self; Novo Nordisk. L. Andersen: None. D. M. Jensen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S, Other Relationship; Self; Novo Nordisk A/S. E. R. Mathiesen: Advisory Panel; Self; Novo Nordisk, Research Support; Self; Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Sanofi-Aventis.