Trial Outcomes & Findings for Efficacy and Safety of Insulin Detemir Versus Neutral Protamine Hagedorn (NPH) Insulin in Pregnant Women With Type 1 Diabetes (NCT NCT00474045)

NCT ID: NCT00474045

Last Updated: 2017-03-10

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 470 participants
• Primary outcome timeframe: At gestational week (GW) 36
• Results posted on: 2017-03-10

Participant Flow

Trial was conducted at 79 sites in 17 countries: Denmark, Finland, France, Ireland, United Kingdom, Norway, Croatia, Poland, Austria, Spain, Canada, Argentina, Brazil, South Africa, Russia, Israel and Australia.

Non-pregnant women were randomised immediately after it was established that they fulfilled the eligibility criteria. Thus, they were exposed to insulin detemir (IDet) throughout organogenesis. Pregnant subjects were to be randomised after completion of the 8th gestational week (GW) and before the completion of 12th GW

Participant milestones

Measure	Insulin Detemir Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Overall Study STARTED	233	237
Overall Study Exposed-All Subjects	233	232
Overall Study Exposed-Pregnant Subjects	152	158
Overall Study Pregnancies (for Exposed-pregnant)	152	160
Overall Study COMPLETED	127	136
Overall Study NOT COMPLETED	106	101

Reasons for withdrawal

Measure	Insulin Detemir Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Overall Study Adverse Event	18	8
Overall Study Unclassified	1	3
Overall Study Lack of Efficacy	0	9
Overall Study Lost to Follow-up	1	1
Overall Study Protocol Violation	10	12
Overall Study Withdrawal by Subject	16	18
Overall Study Withdrawal criteria	60	50

Baseline Characteristics

Efficacy and Safety of Insulin Detemir Versus Neutral Protamine Hagedorn (NPH) Insulin in Pregnant Women With Type 1 Diabetes

Baseline characteristics by cohort

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Total n=310 Participants Total of all reporting groups
Age, Continuous	29.7 years STANDARD_DEVIATION 4.62 • n=5 Participants	30.4 years STANDARD_DEVIATION 4.21 • n=7 Participants	30.1 years STANDARD_DEVIATION 4.43 • n=5 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	158 Participants n=7 Participants	310 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized White	135 participants n=5 Participants	142 participants n=7 Participants	277 participants n=5 Participants
Race/Ethnicity, Customized Unknown	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Height	1.67 meters STANDARD_DEVIATION 0.07 • n=5 Participants	1.65 meters STANDARD_DEVIATION 0.06 • n=7 Participants	1.66 meters STANDARD_DEVIATION 0.07 • n=5 Participants
Body Weight	67.6 kg STANDARD_DEVIATION 12.3 • n=5 Participants	68.7 kg STANDARD_DEVIATION 12.4 • n=7 Participants	68.2 kg STANDARD_DEVIATION 12.3 • n=5 Participants
Body Mass Index (BMI)	24.34 kg/m^2 STANDARD_DEVIATION 3.95 • n=5 Participants	25.17 kg/m^2 STANDARD_DEVIATION 4.22 • n=7 Participants	24.76 kg/m^2 STANDARD_DEVIATION 4.1 • n=5 Participants
Smoker No	143 participants n=5 Participants	147 participants n=7 Participants	290 participants n=5 Participants
Smoker Yes	9 participants n=5 Participants	11 participants n=7 Participants	20 participants n=5 Participants
Daily Use of Alcohol No	150 participants n=5 Participants	158 participants n=7 Participants	308 participants n=5 Participants
Daily Use of Alcohol Yes	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Stratification Pregnant after Randomisation	73 participants n=5 Participants	75 participants n=7 Participants	148 participants n=5 Participants
Stratification Pregnant at Randomisation	79 participants n=5 Participants	83 participants n=7 Participants	162 participants n=5 Participants
Glycosylated Haemoglobin (HbA1c)	6.95 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.82 • n=5 Participants	7.08 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.76 • n=7 Participants	7.01 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.79 • n=5 Participants
Fasting Plasma Glucose (FPG)	5.89 mmol/L STANDARD_DEVIATION 3.29 • n=5 Participants	5.99 mmol/L STANDARD_DEVIATION 3.23 • n=7 Participants	5.94 mmol/L STANDARD_DEVIATION 3.25 • n=5 Participants
Diabetes History	11.72 years STANDARD_DEVIATION 8.08 • n=5 Participants	12.78 years STANDARD_DEVIATION 7.94 • n=7 Participants	12.26 years STANDARD_DEVIATION 8.02 • n=5 Participants

PRIMARY outcome

Timeframe: At gestational week (GW) 36

Population: Full Analysis Set (FAS) for pregnant subjects-all randomised subjects exposed to at least 1 dose of trial drug and pregnant during trial. IDet (N)=152 and NPH (N)=158. Missing values were imputed using Last observation carried forward (LOCF). For FAS, LOCF was made using the pregnancy visits, the early termination visit and the withdrawal visit.

Outcome measures

Measure	Insulin Detemir n=138 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=145 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36	6.27 Percent (%) glycosylated haemoglobin Standard Error 0.053	6.33 Percent (%) glycosylated haemoglobin Standard Error 0.052

PRIMARY outcome

Timeframe: At gestational week (GW) 36

Population: Per Protocol Analysis Set (pregnant subjects): comprised all subjects from the FAS (pregnant subjects) except subjects who significantly violated the inclusion/exclusion criteria. Gestational age at delivery must be at least 32 completed weeks.

Outcome measures

Measure	Insulin Detemir n=127 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=135 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36	6.22 Percent (%) glycosylated haemoglobin Standard Error 0.069	6.37 Percent (%) glycosylated haemoglobin Standard Error 0.067

SECONDARY outcome

Timeframe: During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Delivery Visit (end of pregnancy)] and Follow-Up Visit ( 6 weeks after delivery)

Population: Full Analysis Set (FAS) for pregnant subjects-all randomised subjects exposed to at least 1 dose of trial drug and pregnant during trial. IDet (N)=152 and NPH (N)=158. Missing values were imputed using Last observation carried forward (LOCF). For FAS, LOCF was made using the pregnancy visits, the early termination visit and the withdrawal visit.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Glycosylated Haemoglobin (HbA1c) During Pregnancy GW 8-12 IDet (N)=140, NPH (N)=146	6.6 Percent (%) glycosylated haemoglobin Standard Deviation 0.8	6.8 Percent (%) glycosylated haemoglobin Standard Deviation 0.7
Glycosylated Haemoglobin (HbA1c) During Pregnancy GW 14 IDet (N)=136, NPH (N)=146	6.3 Percent (%) glycosylated haemoglobin Standard Deviation 0.7	6.5 Percent (%) glycosylated haemoglobin Standard Deviation 0.7
Glycosylated Haemoglobin (HbA1c) During Pregnancy GW 24 IDet (N)=138, NPH (N)=146	6 Percent (%) glycosylated haemoglobin Standard Deviation 0.7	6.1 Percent (%) glycosylated haemoglobin Standard Deviation 0.8
Glycosylated Haemoglobin (HbA1c) During Pregnancy GW 36 IDet (N)=138, NPH (N)=146	6.2 Percent (%) glycosylated haemoglobin Standard Deviation 0.8	6.3 Percent (%) glycosylated haemoglobin Standard Deviation 0.8
Glycosylated Haemoglobin (HbA1c) During Pregnancy Delivery IDet (N)=138, NPH (N)=146	6.3 Percent (%) glycosylated haemoglobin Standard Deviation 0.7	6.5 Percent (%) glycosylated haemoglobin Standard Deviation 1.0
Glycosylated Haemoglobin (HbA1c) During Pregnancy Follow-up IDet (N)=138, NPH (N)=146	6.5 Percent (%) glycosylated haemoglobin Standard Deviation 0.9	6.6 Percent (%) glycosylated haemoglobin Standard Deviation 0.8

SECONDARY outcome

Timeframe: At both Visit P3 (GW 24) and Visit P4 (GW 36)

Population: FAS for pregnant subjects-all randomised subjects exposed to at least 1 dose of trial drug and pregnant during trial. IDet (N)=152 and NPH (N)=158. Missing values were imputed using LOCF which was made using pregnancy visits, early termination visit and withdrawal visit. Analysed subjects-subjects with valid HbA1c values at visit P3 and P4.

Outcome measures

Measure	Insulin Detemir n=138 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=146 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Subjects Reaching HbA1c at or Below 6.0% Both at GW 24 and GW 36	57 participants	46 participants

SECONDARY outcome

Timeframe: During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)]

Population: Full Analysis Set (FAS) for pregnant subjects-all randomised subjects exposed to at least 1 dose of trial drug and pregnant during trial. IDet (N)=152 and NPH (N)=158. Missing values were imputed using Last observation carried forward (LOCF). For FAS, LOCF was made using the pregnancy visits, the early termination visit and the withdrawal visit.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Fasting Plasma Glucose (FPG) GW 8-12 IDet (N)=130, NPH (N)=141	5.0 mmol/L Standard Deviation 2.3	5.8 mmol/L Standard Deviation 3.0
Fasting Plasma Glucose (FPG) GW 14 IDet (N)=125, NPH (N)=135	5.0 mmol/L Standard Deviation 3.0	5.7 mmol/L Standard Deviation 2.7
Fasting Plasma Glucose (FPG) GW 24 IDet (N)=129, NPH (N)=141	5.2 mmol/L Standard Deviation 2.4	6.3 mmol/L Standard Deviation 3.3
Fasting Plasma Glucose (FPG) GW 36 IDet (N)=129, NPH (N)=142	4.7 mmol/L Standard Deviation 1.9	5.4 mmol/L Standard Deviation 2.3

SECONDARY outcome

Timeframe: Visit P3 (GW 24)

Population: Full Analysis Set (FAS) for pregnant subjects-all randomised subjects exposed to at least 1 dose of trial drug and pregnant during trial. IDet (N)=152 \& NPH (N)=158. Missing values were imputed using Last observation carried forward (LOCF). For FAS, LOCF was made using the average values.

8-point SMPG was recorded 3 times prior to each visit, and the average value for each of the 8-time points was applied when presenting and analysing the SMPG data. Visit reallocation was made for the early termination visit and for the withdrawal visit.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 120 mins after Dinner (N=117,133)	7.2 mmol/L Standard Deviation 2.0	7.8 mmol/L Standard Deviation 2.1
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 Bedtime (N=125,137)	7.6 mmol/L Standard Deviation 2.4	7.8 mmol/L Standard Deviation 2.2
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 Before Breakfast (N=131,141)	6.4 mmol/L Standard Deviation 1.9	7.3 mmol/L Standard Deviation 2.0
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 120 mins after breakfast (N=130,141)	7.7 mmol/L Standard Deviation 2.3	8.0 mmol/L Standard Deviation 2.2
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 Before Lunch (N=131,141)	6.1 mmol/L Standard Deviation 1.9	6.7 mmol/L Standard Deviation 2.1
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 120 mins after lunch (N=130,140)	7.2 mmol/L Standard Deviation 1.9	7.4 mmol/L Standard Deviation 2.1
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 Before Dinner (N=130,140)	6.8 mmol/L Standard Deviation 2.0	7.0 mmol/L Standard Deviation 2.1
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 At 2.00 A.M. (N=125,134)	6.7 mmol/L Standard Deviation 2.1	6.9 mmol/L Standard Deviation 2.3

SECONDARY outcome

Timeframe: Visit P4 (GW 36)

Population: Full Analysis Set (FAS) for pregnant subjects-all randomised subjects exposed to at least 1 dose of trial drug and pregnant during trial. IDet (N)=152 \& NPH (N)=158. Missing values were imputed using Last observation carried forward (LOCF). For FAS, LOCF was made using the average values.

8-point SMPG was recorded 3 times prior to each visit, and the average value for each of the 8-time points was applied when presenting and analysing the SMPG data. Visit reallocation was made for the early termination visit and for the withdrawal visit.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 Before Breakfast (N=131,141)	6 mmol/L Standard Deviation 1.7	6.3 mmol/L Standard Deviation 1.6
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 120 mins after breakfast (N=130,139)	7.4 mmol/L Standard Deviation 2	7.5 mmol/L Standard Deviation 1.9
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 Before Lunch (N=131,141)	5.9 mmol/L Standard Deviation 1.7	6.1 mmol/L Standard Deviation 1.9
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 120 mins after lunch (N=130,140)	6.9 mmol/L Standard Deviation 1.7	7.1 mmol/L Standard Deviation 2.1
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 Before Dinner (N=131,140)	6.5 mmol/L Standard Deviation 1.7	6.5 mmol/L Standard Deviation 1.9
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 120 mins after Dinner (N=117,132)	7.4 mmol/L Standard Deviation 2.1	7.4 mmol/L Standard Deviation 1.9
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 Bedtime (N=126,137)	7 mmol/L Standard Deviation 1.8	7.2 mmol/L Standard Deviation 2
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 At 2.00 A.M. (N=122,135)	6 mmol/L Standard Deviation 1.8	6.4 mmol/L Standard Deviation 1.8

SECONDARY outcome

Timeframe: Participants were followed during the pregnancy period, an average of 9.6 months

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

AE=any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product. Related AE=relationship of probable or possible. Serious adverse event (SAE) =any undesirable serious medical event as defined in protocol.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Number of Subjects With Adverse Events (AEs) Subjects with AEs leading to withdrawal	13 participants	6 participants
Maternal Safety - Number of Subjects With Adverse Events (AEs) Subjects with (w.) adverse events	138 participants	141 participants
Maternal Safety - Number of Subjects With Adverse Events (AEs) Subjects with serious adverse events	61 participants	49 participants
Maternal Safety - Number of Subjects With Adverse Events (AEs) Subjects with severe adverse events	38 participants	32 participants
Maternal Safety - Number of Subjects With Adverse Events (AEs) Subjects w. AEs related to basal insulin	18 participants	16 participants
Maternal Safety - Number of Subjects With Adverse Events (AEs) Subjects w. AEs related to bolus insulin	12 participants	14 participants

SECONDARY outcome

Timeframe: Foetuses/Newborns were followed during the pregnancy period, an average of 9.6 months and Follow-Up period (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Each pregnant woman analyzed had exactly one Foetus/Newborn that was analyzed for AEs.

AE=any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product. Related AE=relationship of probable or possible. SAE=any undesirable serious medical event as defined in protocol.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events Subjects w. AEs related to Bolus insulin	1 Foetus/Newborns (1 per pregnant woman)	0 Foetus/Newborns (1 per pregnant woman)
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events Subjects with AEs leading to withdrawal	0 Foetus/Newborns (1 per pregnant woman)	1 Foetus/Newborns (1 per pregnant woman)
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events Subjects with adverse events	56 Foetus/Newborns (1 per pregnant woman)	55 Foetus/Newborns (1 per pregnant woman)
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events Subjects with serious adverse events	36 Foetus/Newborns (1 per pregnant woman)	32 Foetus/Newborns (1 per pregnant woman)
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events Subjects with severe adverse events	15 Foetus/Newborns (1 per pregnant woman)	12 Foetus/Newborns (1 per pregnant woman)
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events Subjects w. AEs related to Basal insulin	1 Foetus/Newborns (1 per pregnant woman)	0 Foetus/Newborns (1 per pregnant woman)

SECONDARY outcome

Timeframe: Participants were followed during the pregnancy period, an average of 9.6 months

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

All episodes include major, minor and symptoms only. Major episode : unable to self-treat. Minor: able to self-treat and plasma glucose (PG) < 3.1 mmol/L. Symptoms only: able to self-treat and no PG measurement or PG glucose ≥3.1 mmol/L. Diurnal: Episode occurring between 06.00 - 00.00, both including.

Outcome measures

Measure	Insulin Detemir n=144 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=146 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Hypoglycaemic Episodes All Episodes	9496 episodes	9453 episodes
Maternal Safety - Hypoglycaemic Episodes Diurnal	8045 episodes	7810 episodes

SECONDARY outcome

Timeframe: Participants were followed during the pregnancy period, an average of 9.6 months

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

A nocturnal episode is any episode occurring between 0.01 - 5.59, both including. It includes major, minor and symptoms only episodes. Major: unable to self-treat. Minor: able to self-treat and plasma glucose (PG) < 3.1 mmol/L. Symptoms only: able to self-treat and no PG measurement or PG glucose ≥3.1 mmol/L.

Outcome measures

Measure	Insulin Detemir n=119 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=130 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Nocturnal Hypoglycaemic Episodes	1451 episodes	1643 episodes

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in albumin level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Albumin Serum Level (Biochemistry) Visit P1 IDet (N)=138, NPH (N)=145	4.05 g/dL Standard Deviation 0.22	4.04 g/dL Standard Deviation 0.23
Maternal Safety - Change in Albumin Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	4.19 g/dL Standard Deviation 0.25	4.12 g/dL Standard Deviation 0.27
Maternal Safety - Change in Albumin Serum Level (Biochemistry) Change from Visit P1-FU (N=136, 145)	0.13 g/dL Standard Deviation 0.26	0.09 g/dL Standard Deviation 0.26

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in alanine aminotransferase level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry) Change from Visit P1-FU (N=136, 145)	10.88 U/L Standard Deviation 17.51	8.16 U/L Standard Deviation 15.6
Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry) Visit P1 IDet (N)=138, NPH (N)=145	16.12 U/L Standard Deviation 11.31	17.97 U/L Standard Deviation 9.53
Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	27.06 U/L Standard Deviation 14.92	26.16 U/L Standard Deviation 14.21

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in alkaline phosphatase level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry) Visit P1 IDet (N)=137, NPH (N)=144	52.64 U/L Standard Deviation 13.63	53.88 U/L Standard Deviation 13.75
Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	90.17 U/L Standard Deviation 26.68	92.96 U/L Standard Deviation 28.07
Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry) Change from Visit P1-FU (N=135, 144)	37.39 U/L Standard Deviation 20.86	39.51 U/L Standard Deviation 23.34

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in creatinine serum level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Creatinine Serum Level (Biochemistry) Change from Visit P1-FU (N=136, 145)	11.18 mcmol/L Standard Deviation 7.61	12.52 mcmol/L Standard Deviation 8.67
Maternal Safety - Change in Creatinine Serum Level (Biochemistry) Visit P1 IDet (N)=138, NPH (N)=145	52.04 mcmol/L Standard Deviation 7.85	54.01 mcmol/L Standard Deviation 8.81
Maternal Safety - Change in Creatinine Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	62.98 mcmol/L Standard Deviation 9.73	66.57 mcmol/L Standard Deviation 11.8

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in lactate dehydrogenase serum level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry) Visit P1 IDet (N)=138, NPH (N)=145	145.1 U/L Standard Deviation 34.11	144.1 U/L Standard Deviation 24.6
Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	167.5 U/L Standard Deviation 29.29	169.5 U/L Standard Deviation 33.75
Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry) Change from Visit P1-FU (N=136, 145)	21.82 U/L Standard Deviation 33.61	25.46 U/L Standard Deviation 30.48

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in potassium serum level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Potassium Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	4.30 mmol/L Standard Deviation 0.33	4.31 mmol/L Standard Deviation 0.34
Maternal Safety - Change in Potassium Serum Level (Biochemistry) Visit P1 IDet (N)=137, NPH (N)=144	4.13 mmol/L Standard Deviation 0.32	4.12 mmol/L Standard Deviation 0.27
Maternal Safety - Change in Potassium Serum Level (Biochemistry) Change from Visit P1-FU (N=135, 144)	0.15 mmol/L Standard Deviation 0.36	0.20 mmol/L Standard Deviation 0.36

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in sodium serum level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Sodium Serum Level (Biochemistry) Change from Visit P1-FU (N=135, 145)	3.59 mmol/L Standard Deviation 3.19	3.36 mmol/L Standard Deviation 3.27
Maternal Safety - Change in Sodium Serum Level (Biochemistry) Visit P1 IDet (N)=137, NPH (N)=145	138.0 mmol/L Standard Deviation 2.19	137.8 mmol/L Standard Deviation 2.36
Maternal Safety - Change in Sodium Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	141.6 mmol/L Standard Deviation 2.57	141.2 mmol/L Standard Deviation 2.71

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in total protein serum level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Total Protein Serum Level (Biochemistry) Visit P1 IDet (N)=138, NPH (N)=145	6.84 g/dL Standard Deviation 0.37	6.89 g/dL Standard Deviation 0.42
Maternal Safety - Change in Total Protein Serum Level (Biochemistry) FU Visit IDet (N)=138, NPH (N)=146	7.08 g/dL Standard Deviation 0.44	7.11 g/dL Standard Deviation 0.47
Maternal Safety - Change in Total Protein Serum Level (Biochemistry) Change from Visit P1-FU (N=136, 145)	0.24 g/dL Standard Deviation 0.42	0.22 g/dL Standard Deviation 0.39

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in haemoglobin level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Haemoglobin Level (Haematology) Visit P1 IDet (N)=138, NPH (N)=146	7.64 mmol/L Standard Deviation 0.48	7.64 mmol/L Standard Deviation 0.5
Maternal Safety - Change in Haemoglobin Level (Haematology) FU Visit IDet (N)=138, NPH (N)=146	7.81 mmol/L Standard Deviation 0.57	7.69 mmol/L Standard Deviation 0.57
Maternal Safety - Change in Haemoglobin Level (Haematology) Change from Visit P1-FU (N=136, 145)	0.16 mmol/L Standard Deviation 0.57	0.05 mmol/L Standard Deviation 0.6

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in leukocytes level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Leukocytes Level (Haematology) Visit P1 IDet (N)=138, NPH (N)=146	8.01 10^9 cells/L Standard Deviation 2.21	8.2 10^9 cells/L Standard Deviation 2.04
Maternal Safety - Change in Leukocytes Level (Haematology) FU Visit IDet (N)=138, NPH (N)=146	6.68 10^9 cells/L Standard Deviation 1.79	6.55 10^9 cells/L Standard Deviation 1.92
Maternal Safety - Change in Leukocytes Level (Haematology) Change from Visit P1-FU (N=136, 145)	-1.36 10^9 cells/L Standard Deviation 1.93	-1.65 10^9 cells/L Standard Deviation 2.12

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in thrombocytes level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Thrombocytes Level (Haematology) Visit P1 IDet (N)=138, NPH (N)=146	245.3 10^9 cells/L Standard Deviation 48.27	247.2 10^9 cells/L Standard Deviation 59.32
Maternal Safety - Change in Thrombocytes Level (Haematology) FU Visit IDet (N)=138, NPH (N)=146	270.6 10^9 cells/L Standard Deviation 66.01	263.1 10^9 cells/L Standard Deviation 68.12
Maternal Safety - Change in Thrombocytes Level (Haematology) Change from Visit P1-FU (N=136, 145)	24.25 10^9 cells/L Standard Deviation 55.07	16.16 10^9 cells/L Standard Deviation 52.02

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and calculated as an estimate of the mean change from Visit P1 in urine albumin level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Urine Albumin Level (Urinalysis) FU Visit IDet (N)=138, NPH (N)=146	0.02 g/dL Standard Deviation 0.04	0.03 g/dL Standard Deviation 0.12
Maternal Safety - Change in Urine Albumin Level (Urinalysis) Change from Visit P1-FU (N=133, 142)	0.01 g/dL Standard Deviation 0.04	0.02 g/dL Standard Deviation 0.11
Maternal Safety - Change in Urine Albumin Level (Urinalysis) Visit P1 IDet (N)=135, NPH (N)=143	0.01 g/dL Standard Deviation 0.02	0.01 g/dL Standard Deviation 0.02

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and calculated as an estimate of the mean change from Visit P1 in albumin/creatinine ratio at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis) Visit P1 IDet (N)=135, NPH (N)=143	0.82 mg/mmol Standard Deviation 1.4	0.85 mg/mmol Standard Deviation 1.65
Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis) FU Visit IDet (N)=138, NPH (N)=146	2.65 mg/mmol Standard Deviation 5.6	4.81 mg/mmol Standard Deviation 32.22
Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis) Change from Visit P1-FU (N=133, 142)	1.88 mg/mmol Standard Deviation 5.29	4.07 mg/mmol Standard Deviation 32.43

SECONDARY outcome

Timeframe: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing data was imputed using LOCF.

This is the standard safety lab parameter and calculated as an estimate of the mean change from Visit P1 in Urine-N (creatinine) level at Follow-Up Visit (6 weeks after delivery).

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Urine N (Creatinine) (Urinalysis) Visit P1 IDet (N)=135, NPH (N)=144	114.8 mg/dL Standard Deviation 63.77	103.1 mg/dL Standard Deviation 56.37
Maternal Safety - Change in Urine N (Creatinine) (Urinalysis) FU Visit IDet (N)=138, NPH (N)=146	106.2 mg/dL Standard Deviation 66.44	98.61 mg/dL Standard Deviation 58.71
Maternal Safety - Change in Urine N (Creatinine) (Urinalysis) Change from Visit P1-FU (N=133, 143)	-6.62 mg/dL Standard Deviation 83.83	-6.34 mg/dL Standard Deviation 70.79

SECONDARY outcome

Timeframe: Baseline, Visit P4 (GW 36). Baseline is Visit 2 (randomisation visit, within 3 weeks of screening) for subjects not pregnant at randomisation and Visit P1 (GW 8-12) for pregnant subjects at randomisation.

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Change in concentrations of values for insulin detemir specific antibodies from baseline to Visit P4 was calculated. The unit for measuring antibody levels is amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture (%B/T). Samples were taken before 1st dosing.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Insulin Detemir Specific Antibodies Baseline IDet (N)=145, NPH (N)=155	1.13 %B/T Interval -0.1 to 6.55	1.09 %B/T Interval -1.36 to 7.35
Maternal Safety - Change in Insulin Detemir Specific Antibodies Visit P4 IDet (N)=110, NPH (N)=110	1.36 %B/T Interval -0.64 to 12.71	1.25 %B/T Interval -3.64 to 6.74
Maternal Safety - Change in Insulin Detemir Specific Antibodies Change from Baseline-Visit P4(N=105,109)	0.04 %B/T Interval -3.89 to 12.11	0.09 %B/T Interval -5.93 to 6.26

SECONDARY outcome

Timeframe: Baseline, Visit P4 (GW 36). Baseline is Visit 2 (randomisation visit, within 3 weeks of screening) for subjects not pregnant at randomisation and Visit P1 (GW 8-12) for pregnant subjects at randomisation.

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Change in concentrations values for insulin aspart specific antibodies from baseline to Visit P4 was calculated. The unit for measuring antibody levels is amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture (%B/T). Samples were taken before 1st dosing.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Insulin Aspart Specific Antibodies Visit P4 IDet (N)=109, NPH (N)=110	0.43 %B/T Interval -0.58 to 22.34	0.36 %B/T Interval -0.52 to 52.23
Maternal Safety - Change in Insulin Aspart Specific Antibodies Baseline IDet (N)=145, NPH (N)=154	0.44 %B/T Interval -0.25 to 29.74	0.46 %B/T Interval -0.39 to 55.73
Maternal Safety - Change in Insulin Aspart Specific Antibodies Change from Baseline-Visit P4(N=104,109)	-0.12 %B/T Interval -8.63 to 10.1	-0.21 %B/T Interval -11.6 to 2.11

SECONDARY outcome

Timeframe: Baseline, Visit P4 (GW 36). Baseline is Visit 2 (randomisation visit, within 3 weeks of screening) for subjects not pregnant at randomisation and Visit P1 (GW 8-12) for pregnant subjects at randomisation.

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Change in concentrations values for insulin detemir/aspart cross-reacting antibodies from baseline to Visit P4 was calculated. The unit for measuring antibody levels is amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture (%B/T). Samples were taken before 1st dosing

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies Change from Baseline-Visit P4(N=106,109)	-0.43 %B/T Interval -43.3 to 39.43	-1.12 %B/T Interval -27.9 to 14.52
Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies Baseline IDet (N)=146, NPH (N)=155	5.21 %B/T Interval -0.02 to 76.75	5.36 %B/T Interval -0.5 to 67.4
Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies Visit P4 IDet (N)=110, NPH (N)=110	5.40 %B/T Interval -0.21 to 50.37	4.28 %B/T Interval -0.22 to 62.25

SECONDARY outcome

Timeframe: At Delivery (End of Pregnancy)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).

Outcome measures

Measure	Insulin Detemir n=104 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=118 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood	1.31 %B/T Interval -0.43 to 13.74	0.90 %B/T Interval -2.48 to 3.23

SECONDARY outcome

Timeframe: At Delivery (End of Pregnancy)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T)

Outcome measures

Measure	Insulin Detemir n=103 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=118 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood	0.38 %B/T Interval -0.87 to 19.27	0.32 %B/T Interval -0.45 to 11.08

SECONDARY outcome

Timeframe: At Delivery (End of Pregnancy)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).

Outcome measures

Measure	Insulin Detemir n=104 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=119 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood	5.99 %B/T Interval 0.06 to 49.67	4.12 %B/T Interval 0.05 to 74.59

SECONDARY outcome

Timeframe: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)

Outcome measures

Measure	Insulin Detemir n=94 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=96 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies	1.10 ratio Interval -39.2 to 8.8	0.77 ratio Interval -4.2 to 7.5

SECONDARY outcome

Timeframe: At Delivery

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. IDet in cord blood was analysed for subjects in the IDet Arm and only for 98 subjects, as for 72 subjects it was reported as below measuring range (\<25.00 pmol/L).

Outcome measures

Measure	Insulin Detemir n=98 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood	25.00 pmol/L Interval 25.0 to 209.6	—

SECONDARY outcome

Timeframe: Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing values were imputed using LOCF.

Change in the body weight was summarised by treatment.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit GW (8-12) IDet(N)=139,NPH(N)=145	67.8 kg Standard Deviation 11.6	69.2 kg Standard Deviation 12.5
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit Change from GW(8-12)-GW 14 (N=128,139)	1.0 kg Standard Deviation 1.6	1.4 kg Standard Deviation 1.9
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit Change from GW(8-12)-GW 24 (N=130,139)	5.6 kg Standard Deviation 2.7	6.0 kg Standard Deviation 3.2
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit Change from GW(8-12)-GW 36(N=130,139)	11.5 kg Standard Deviation 4.2	11.0 kg Standard Deviation 5.2

SECONDARY outcome

Timeframe: Visit P1 (GW (8-12)), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing values were imputed using LOCF.

Change in the systolic blood pressure was summarised by treatment.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit GW (8-12) IDet(N)=140,NPH(N)=146	114.1 mmHg Standard Deviation 11.4	116.2 mmHg Standard Deviation 10.4
Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-GW 14 (N=137,145)	0.8 mmHg Standard Deviation 10.1	-2.8 mmHg Standard Deviation 9.6
Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-GW 24(N=138,145)	-0.7 mmHg Standard Deviation 9.6	-1.6 mmHg Standard Deviation 11.3
Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-GW 36(N=138,145)	3.1 mmHg Standard Deviation 11.3	2.3 mmHg Standard Deviation 11.8
Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-FU(N=138,145)	2.6 mmHg Standard Deviation 11.6	-0 mmHg Standard Deviation 12.5

SECONDARY outcome

Timeframe: Visit P1 (GW (8-12)), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (FU) Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing values were imputed using LOCF.

Change in the diastolic blood pressure was summarised by treatment.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit GW (8-12) IDet(N)=140,NPH(N)=146	70.5 mmHg Standard Deviation 8.9	70.7 mmHg Standard Deviation 8.2
Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-GW 14 (N=137,145)	-0.2 mmHg Standard Deviation 8.4	-0.5 mmHg Standard Deviation 9.1
Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-GW 24(N=138,145)	-1.6 mmHg Standard Deviation 8.7	-1.2 mmHg Standard Deviation 9.3
Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-GW 36(N=138,145)	3.2 mmHg Standard Deviation 9.9	2.6 mmHg Standard Deviation 11.0
Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit Change from GW(8-12)-FU(N=138,145)	1.3 mmHg Standard Deviation 9.5	1.8 mmHg Standard Deviation 9.8

SECONDARY outcome

Timeframe: Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up Visit (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Missing values were imputed using LOCF.

Change in the pulse was summarised by treatment.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up Change from GW(8-12)-GW 14 (N=133,139)	1.5 beats/minute Standard Deviation 9.3	2.2 beats/minute Standard Deviation 10
Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up Change from GW(8-12)-GW 24(N=134,141)	3.5 beats/minute Standard Deviation 10.6	4.5 beats/minute Standard Deviation 10.6
Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up GW (8-12) IDet(N)=136,NPH(N)=142	77.4 beats/minute Standard Deviation 10	76.8 beats/minute Standard Deviation 9.6
Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up Change from GW(8-12)-GW 36(N=134,141)	5.2 beats/minute Standard Deviation 11.8	4.9 beats/minute Standard Deviation 12
Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up Change from GW(8-12)-FU(N=134,141)	-3 beats/minute Standard Deviation 11.7	-2.3 beats/minute Standard Deviation 11.9

SECONDARY outcome

Timeframe: Follow-Up (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

The number of subjects having a electrocardiogram (ECG) that changed from 'Normal' or 'Abnormal, not clinically significant' (at Visit 1, 3 weeks before randomisation) to 'Abnormal, clinically significant' (at Follow-Up). 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Electrocardiogram (ECG)	0 participants	0 participants

SECONDARY outcome

Timeframe: From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Acceleration of retinopathy was summarised by treatment and missing data was imputed using LOCF.

Acceleration of Retinopathy is defined as worsening of fundoscopy/fundusphotography findings from GW 8-12 (Visit P1) to follow-up on one or both eyes.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Acceleration of Retinopathy in Any Eye Acceleration in Any Eye	12 participants	14 participants
Maternal Safety - Acceleration of Retinopathy in Any Eye No Acceleration in Any Eye	120 participants	120 participants
Maternal Safety - Acceleration of Retinopathy in Any Eye Missing Data	20 participants	24 participants

SECONDARY outcome

Timeframe: From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. Acceleration of nephropathy was summarised by treatment and missing data was imputed using LOCF.

Acceleration of nephropathy was defined as a change from a low U-albumin:U-creatinine ratio ≤33.93 mg/mmol to a high U-albumin:U-creatinine ratio > 33.93 mg/mmol from GW 8-12 (Visit P1) to the follow-up visit.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Acceleration of Nephropathy	2 participants	1 participants

SECONDARY outcome

Timeframe: At Delivery Visit

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial. This set in total contains 152 subjects in IDet and 158 subjects in NPH arm. The partcipant analysed for this outcome measure are the number of subjects at delivery visit.

Non-Planned Caesarean Section is a procedure which takes place ≤8h prior to delivery. Planned Caesarean Section takes place >8h prior to delivery.

Outcome measures

Measure	Insulin Detemir n=130 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=136 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Maternal Safety - Mode of Delivery Spontaneous onset of labour (N)=130,136	19 percentage (%) of subjects	28 percentage (%) of subjects
Maternal Safety - Mode of Delivery Induction of labour (N)=130,136	39 percentage (%) of subjects	36 percentage (%) of subjects
Maternal Safety - Mode of Delivery Normal Vaginal Delivery(N)=54,50	76 percentage (%) of subjects	80 percentage (%) of subjects
Maternal Safety - Mode of Delivery Instrumental Vaginal Delivery(N)=54,50	24 percentage (%) of subjects	20 percentage (%) of subjects
Maternal Safety - Mode of Delivery Non-Planned Caesarean Section(N)=76,86	36 percentage (%) of subjects	43 percentage (%) of subjects
Maternal Safety - Mode of Delivery Planned Caesarean Section(N)=76,86	65 percentage (%) of subjects	57 percentage (%) of subjects

SECONDARY outcome

Timeframe: Delivery Visit

Population: Safety analysis set (pregnant subjects): randomised subjects exposed to at least 1 dose of trial product and preg. during the trial. IDet (N)=152 (152 pregnancies) NPH (N)=158 subjects (160 pregnancies, 2 subjects had spontaneous abortion and became preg. again). Analysed subjects-no. of subjects with a preg. outcome at delivery visit.

Induced abortion means interruption of a living pregnancy < 22 completed weeks. Early foetal death means death before 22 completed GWs. Stillbirth indicates death between at or after 22 GW and at or before delivery.

Outcome measures

Measure	Insulin Detemir n=142 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=145 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Pregnancy Outcome at Delivery Early Foetal Death (Spont. Abortion)	10 participants	8 participants
Pregnancy Outcome at Delivery Stillbirth	2 participants	0 participants
Pregnancy Outcome at Delivery Live Birth	128 participants	136 participants
Pregnancy Outcome at Delivery Early Foetal Death (Ectopic Pregnancy)	1 participants	1 participants
Pregnancy Outcome at Delivery Induced Abortion	1 participants	0 participants

SECONDARY outcome

Timeframe: Follow-Up (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): randomised subjects exposed to at least 1 dose of trial product and preg. during the trial. IDet (N)=152 (152 pregnancies) NPH (N)=158 subjects (160 pregnancies, 2 subjects had spontaneous abortion and became preg. again). Analysed subjects-no. of subjects with a preg. outcome at delivery visit.

Induced abortion means interruption of a living pregnancy < 22 completed weeks. Early foetal death means death before 22 completed GWs. Perinatal Death means death of a foetus/infant between ≥ 22 completed GWs and < 1 completed week after delivery. Neonatal Death means death between at or after 7 completed days and before 28 completed days after delivery. Death During Follow-Up means death between at or after 28 days after delivery and at or before Follow-Up.

Outcome measures

Measure	Insulin Detemir n=142 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=145 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Pregnancy Outcome at Follow-Up Early Foetal Death (Ectopic Pregnancy)	1 participants	1 participants
Pregnancy Outcome at Follow-Up Perinatal Death	2 participants	1 participants
Pregnancy Outcome at Follow-Up Live Children	128 participants	135 participants
Pregnancy Outcome at Follow-Up Early Foetal Death (Spont. Abortion)	10 participants	8 participants
Pregnancy Outcome at Follow-Up Induced Abortion	1 participants	0 participants
Pregnancy Outcome at Follow-Up Neonatal Death	0 participants	0 participants
Pregnancy Outcome at Follow-Up Death During Follow-Up	0 participants	0 participants

SECONDARY outcome

Timeframe: Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Safety - Total Daily Insulin Dose During Pregnancy GW 24 IDet (N)=128, NPH (N)=137	0.85 U/kg Standard Deviation 0.29	0.84 U/kg Standard Deviation 0.26
Safety - Total Daily Insulin Dose During Pregnancy GW 36 IDet (N)=119, NPH (N)=121	1.17 U/kg Standard Deviation 0.47	1.05 U/kg Standard Deviation 0.35
Safety - Total Daily Insulin Dose During Pregnancy Follow-Up IDet (N)=124, NPH (N)=133	0.53 U/kg Standard Deviation 0.17	0.57 U/kg Standard Deviation 0.2
Safety - Total Daily Insulin Dose During Pregnancy GW 14 IDet (N)=129, NPH (N)=141	0.73 U/kg Standard Deviation 0.23	0.74 U/kg Standard Deviation 0.25

SECONDARY outcome

Timeframe: End of Pregnancy

Population: Safety analysis set (pregnant subjects): randomised subjects exposed to at least 1 dose of trial product and pregnant during the trial. IDet (N)=152 (152 pregnancies) NPH (N)=158 subjects (160 pregnancies, 2 subjects had spontaneous abortion and became pregnant again).

Wt. corresponds to weight of live-born infants. Pre-term delivery: delivery before 37 completed GWs including abortions. Early foetal death: death before 22 completed GWs. Perinatal mortality: death of a foetus/infant between ≥ 22 completed GWs and < 1 completed week after delivery. Neonatal mortality: post-partum after 7 completed days and before 28 completed days after delivery. Major-malformation: a life threatening structural anomaly or one likely to cause significant impairment of health or functional capacity and needs medical or surgical treatment.

Outcome measures

Measure	Insulin Detemir n=152 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Safety - Composite Pregnancy Outcome Wt. below the 10th percentile(N)=128,136	3 participants	1 participants
Safety - Composite Pregnancy Outcome Wt. above the 90th percentile(N)=128,136	59 participants	73 participants
Safety - Composite Pregnancy Outcome Perinatal mortality (N)=130,136	2 participants	1 participants
Safety - Composite Pregnancy Outcome Neonatal mortality (N)=126,135	0 participants	0 participants
Safety - Composite Pregnancy Outcome Compiled(at least 1 of above)(N)=142,145	89 participants	96 participants
Safety - Composite Pregnancy Outcome Pre-term delivery (N)=142,145	39 participants	45 participants
Safety - Composite Pregnancy Outcome Major malformations (N)=142,145	5 participants	1 participants
Safety - Composite Pregnancy Outcome Early foetal death (N)=142,145	11 participants	9 participants

SECONDARY outcome

Timeframe: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)

Outcome measures

Measure	Insulin Detemir n=93 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=95 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies	0.84 ratio Interval -2.85 to 8.0	0.64 ratio Interval -25.5 to 5.0

SECONDARY outcome

Timeframe: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

Population: Safety analysis set (pregnant subjects): all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)

Outcome measures

Measure	Insulin Detemir n=94 Participants Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=98 Participants Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies	1.29 ratio Interval -76.0 to 8.83	0.90 ratio Interval -3.86 to 57.82

Adverse Events

Insulin Detemir

Serious events: 61 serious events

Other events: 138 other events

Deaths: 0 deaths

Neutral Protamine Hagedorn (NPH) Insulin

Serious events: 49 serious events

Other events: 141 other events

Deaths: 0 deaths

Serious adverse events

Measure	Insulin Detemir n=152 participants at risk Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 participants at risk Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Pregnancy, puerperium and perinatal conditions Aborption spontaneous	5.3% 8/152 • Number of events 8 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	2.5% 4/158 • Number of events 4 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	5.3% 8/152 • Number of events 8 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Threatened labour	2.0% 3/152 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	2.5% 4/158 • Number of events 4 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Failed induction of labour	2.0% 3/152 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.9% 3/158 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Blood and lymphatic system disorders Abortion threatened	2.0% 3/152 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Hyperemesis gravidarum	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Gestational hypertension	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Intra-uterine death	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Placenta praevia	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Placenta praevia haemorrhage	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Premature labour	1.3% 2/152 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Premature separation of placenta	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Aborption incomplete	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Blood and lymphatic system disorders Antepartum haemorrhage	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Blighted ovum	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Breech presentation	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Cephalo-pelvic disproportion	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Cervical incompetence	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Imminent abortion	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Labour complication	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Blood and lymphatic system disorders Placental insufficiency	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Polyhydramnios	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Premature rupture of membranes	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Stillbirth	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Uterine contractions abnormal	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Metabolism and nutrition disorders Hypoglycaemia	3.3% 5/152 • Number of events 5 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	3.2% 5/158 • Number of events 12 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Metabolism and nutrition disorders Hypoglycaemic unconsciousness	1.3% 2/152 • Number of events 4 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	4.4% 7/158 • Number of events 9 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	3.3% 5/152 • Number of events 5 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Metabolism and nutrition disorders Diabetic ketoacidosis	2.0% 3/152 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Metabolism and nutrition disorders Hyperglycaemia	1.3% 2/152 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Vomiting	3.3% 5/152 • Number of events 5 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Nausea	1.3% 2/152 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Abdominal pain, upper	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Diarrhoea	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Abdominal pain	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Impaired gastric emptying	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Gastroenteritis	2.6% 4/152 • Number of events 4 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Beta haemolytic streptococcal infection	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Pyelonephritis	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Urinary tract infection	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Urogenital infection bacterial	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Reproductive system and breast disorders Uterine haemorrhage	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Reproductive system and breast disorders Metrorrhagia	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Reproductive system and breast disorders Genital haemorrhage	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Reproductive system and breast disorders Pelvic pain	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Reproductive system and breast disorders Vaginal haematoma	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Nervous system disorders Headache	2.0% 3/152 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Nervous system disorders Migraine	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Injury, poisoning and procedural complications Incorrect dose administered	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	1.3% 2/158 • Number of events 2 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Injury, poisoning and procedural complications Wrong drug administered	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Vascular disorders Hypertension	1.3% 2/152 • Number of events 3 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Eye disorders Retinopathy	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Eye disorders Visual impairment	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
General disorders Device failure	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
General disorders Malaise	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Hepatobiliary disorders Cholestasis of pregnancy	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Hepatobiliary disorders Cytolytic hepatitis	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Social circumstances Inadequate diet	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Social circumstances Social stay hospitalisation	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Investigations Amniotic fluid volume decreased	0.66% 1/152 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.00% 0/158 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Skin and subcutaneous tissue disorders Polymorphic eruption of pregnancy	0.00% 0/152 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	0.63% 1/158 • Number of events 1 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Other adverse events

Measure	Insulin Detemir n=152 participants at risk Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Neutral Protamine Hagedorn (NPH) Insulin n=158 participants at risk Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn
Infections and infestations Nasopharyngitis	29.6% 45/152 • Number of events 82 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	29.7% 47/158 • Number of events 68 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Urinary Tract Infection	11.2% 17/152 • Number of events 19 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	7.6% 12/158 • Number of events 14 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Gastroenteritis	8.6% 13/152 • Number of events 13 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	5.7% 9/158 • Number of events 11 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Upper respiratory tract infection	5.9% 9/152 • Number of events 10 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	8.2% 13/158 • Number of events 17 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Infections and infestations Influenza	5.9% 9/152 • Number of events 12 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	10.1% 16/158 • Number of events 16 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	5.3% 8/152 • Number of events 8 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	6.3% 10/158 • Number of events 10 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Nervous system disorders Headache	28.3% 43/152 • Number of events 109 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	22.2% 35/158 • Number of events 121 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Diarrhoea	13.8% 21/152 • Number of events 27 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	7.0% 11/158 • Number of events 13 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Abdominal Pain	7.2% 11/152 • Number of events 15 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	7.6% 12/158 • Number of events 22 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Abdominal pain upper	7.9% 12/152 • Number of events 14 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	3.2% 5/158 • Number of events 7 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Toothache	4.6% 7/152 • Number of events 9 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	5.7% 9/158 • Number of events 12 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Gastrointestinal disorders Constipation	2.6% 4/152 • Number of events 4 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	7.0% 11/158 • Number of events 11 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Eye disorders Diabetic Retinopathy	3.9% 6/152 • Number of events 6 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	6.3% 10/158 • Number of events 13 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.2% 11/152 • Number of events 13 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	8.2% 13/158 • Number of events 17 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Blood and lymphatic system disorders Anaemia	14.5% 22/152 • Number of events 23 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	14.6% 23/158 • Number of events 24 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.
Vascular disorders Hypertension	3.3% 5/152 • Number of events 5 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.	5.1% 8/158 • Number of events 8 • Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months AEs has been reported for Mother (during the pregnancy) in the safety analysis set for pregnant subjects (Safety-Pregnant) comprising of all randomised subjects who were exposed to at least one dose of trial product and who were pregnant during the trial.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee Novo Nordisk (NN) reserves the right not to release data until specified milestones, e.g. Clinical Trial Report is available. This includes the right not to release interim results, because the release of such information can invalidate the results of the trial. At the end of the trial, one or more manuscripts for publication will be prepared in collaboration between authors and NN. NN reserves the right to postpone publication and communication for a short time to protect intellectual property.
• Publication restrictions are in place

Restriction type: OTHER