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Trial record 20 of 48 for:    cord blood | ( Map: Canada )

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

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ClinicalTrials.gov Identifier: NCT00474045
Recruitment Status : Completed
First Posted : May 16, 2007
Results First Posted : December 5, 2011
Last Update Posted : March 10, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 1
Interventions Drug: insulin detemir
Drug: NPH insulin
Drug: insulin aspart
Enrollment 470
Recruitment Details 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.
Pre-assignment Details 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
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description 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 Subjects who were not pregnant at 52 weeks after randomisation were withdrawn Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from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
Period Title: Overall Study
Started 233 237
Exposed-All Subjects 233 232 [1]
Exposed-Pregnant Subjects 152 158 [2]
Pregnancies (for Exposed-pregnant) 152 160 [3]
Completed 127 136
Not Completed 106 101
Reason Not Completed
Adverse Event             18             8
Unclassified             1             3
Lack of Efficacy             0             9
Lost to Follow-up             1             1
Protocol Violation             10             12
Withdrawal by Subject             16             18
Withdrawal criteria             60             50
[1]
5 withdrawn before treatment initiation
[2]
3 withdrawn before treatment initiation
[3]
2 subjects had spontaneous abortion and became pregnant again
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 152 158 310
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 152 participants 158 participants 310 participants
29.7  (4.62) 30.4  (4.21) 30.1  (4.43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 158 participants 310 participants
Female
152
 100.0%
158
 100.0%
310
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 158 participants 310 participants
American Indian or Alaska Native 0 1 1
Asian 1 3 4
Black or African American 1 0 1
White 135 142 277
Unknown 12 10 22
Other 3 2 5
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 152 participants 158 participants 310 participants
1.67  (0.07) 1.65  (0.06) 1.66  (0.07)
[1]
Measure Description: The number of subjects (N) analysed in the Neutral Protamine Hagedorn (NPH) group was 157 instead of 158.
Body Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 152 participants 158 participants 310 participants
67.6  (12.3) 68.7  (12.4) 68.2  (12.3)
[1]
Measure Description: The number of subjects (N) analysed in the NPH group was 157 instead of 158.
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 152 participants 158 participants 310 participants
24.34  (3.95) 25.17  (4.22) 24.76  (4.1)
[1]
Measure Description: The number of subjects (N) analysed in the NPH group was 157 instead of 158.
Smoker  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 158 participants 310 participants
No 143 147 290
Yes 9 11 20
Daily Use of Alcohol  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 158 participants 310 participants
No 150 158 308
Yes 2 0 2
Stratification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 152 participants 158 participants 310 participants
Pregnant after Randomisation 73 75 148
Pregnant at Randomisation 79 83 162
Glycosylated Haemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percent (%) glycosylated haemoglobin
Number Analyzed 152 participants 158 participants 310 participants
6.95  (0.82) 7.08  (0.76) 7.01  (0.79)
Fasting Plasma Glucose (FPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 152 participants 158 participants 310 participants
5.89  (3.29) 5.99  (3.23) 5.94  (3.25)
[1]
Measure Description: The number of subjects (N) analysed in the insulin detemir (IDet) group was 139 and NPH group was 151 instead of 152 and 158, respectively.Therefore the total number of subjects analysed were 290 instead of 310.
Diabetes History  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 152 participants 158 participants 310 participants
11.72  (8.08) 12.78  (7.94) 12.26  (8.02)
1.Primary Outcome
Title Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36
Hide Description [Not Specified]
Time Frame At gestational week (GW) 36
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 138 145
Least Squares Mean (Standard Error)
Unit of Measure: Percent (%) glycosylated haemoglobin
6.27  (0.053) 6.33  (0.052)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Detemir, Neutral Protamine Hagedorn (NPH) Insulin
Comments Non-inferiority analysis with a null hypothesis stated that the difference between treatments, IDet-NPH, was equal to or larger than the pre-specified non-inferiority margin of 0.4%. In case non-inferiority was established it was also investigated if IDet was superior to NPH with a null hypothesis stating that the difference between IDet and NPH treatment groups is equal to or greater than 0.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority can only be declared if the non-inferiority criterion was fulfilled for both (FAS and Per-protocol) analysis sets. Non-inferiority was declared if the upper limit of the two-sided 95% CI for the estimated treatment difference was below 0.4%.
Statistical Test of Hypothesis P-Value 0.400
Comments P-value for superiority was calculated.
Method Regression, Linear
Comments Treatment, country, pregnancy (preg.) status at randomisation (random.)-fixed. HbA1c at rand.(covariate) & at rand. by preg. status (interaction)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.06
Confidence Interval 95%
-0.21 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.074
Estimation Comments Estimated treatment differences for IDet versus NPH at Visit P4 with the corresponding 95% confidence interval (CI) was calculated. Non-inferiority was established but superiority was not established.
2.Primary Outcome
Title Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36
Hide Description [Not Specified]
Time Frame At gestational week (GW) 36
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 127 135
Least Squares Mean (Standard Error)
Unit of Measure: Percent (%) glycosylated haemoglobin
6.22  (0.069) 6.37  (0.067)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Detemir, Neutral Protamine Hagedorn (NPH) Insulin
Comments Non-inferiority analysis with a null hypothesis stated that the difference between treatments, IDet-NPH, was equal to or larger than the pre-specified non-inferiority margin of 0.4%. In case non-inferiority was established it was also investigated if IDet was superior to NPH with a null hypothesis stating that the difference between IDet and NPH treatment groups is equal to or greater than 0.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority can only be declared if the non-inferiority criterion was fulfilled for both (FAS and Per-protocol) analysis sets. Non-inferiority was declared if the upper limit of the two-sided 95% CI for the estimated treatment difference was below 0.4%.
Statistical Test of Hypothesis P-Value 0.122
Comments P-value for superiority was calculated
Method Regression, Linear
Comments Treatment, country, preg. status at rand.(fixed factors),HbA1c at rand.(covariate),HbA1c at rand. by preg. status (interaction)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval 95%
-0.34 to 0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.096
Estimation Comments Estimated treatment differences for IDet versus NPH at Visit P4 with the corresponding 95% CI was calculated. Non-inferiority was established but superiority was not established.
3.Secondary Outcome
Title Glycosylated Haemoglobin (HbA1c) During Pregnancy
Hide Description [Not Specified]
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: Percent (%) glycosylated haemoglobin
GW 8-12 IDet (N)=140, NPH (N)=146 6.6  (0.8) 6.8  (0.7)
GW 14 IDet (N)=136, NPH (N)=146 6.3  (0.7) 6.5  (0.7)
GW 24 IDet (N)=138, NPH (N)=146 6  (0.7) 6.1  (0.8)
GW 36 IDet (N)=138, NPH (N)=146 6.2  (0.8) 6.3  (0.8)
Delivery IDet (N)=138, NPH (N)=146 6.3  (0.7) 6.5  (1.0)
Follow-up IDet (N)=138, NPH (N)=146 6.5  (0.9) 6.6  (0.8)
4.Secondary Outcome
Title Subjects Reaching HbA1c at or Below 6.0% Both at GW 24 and GW 36
Hide Description [Not Specified]
Time Frame At both Visit P3 (GW 24) and Visit P4 (GW 36)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 138 146
Measure Type: Number
Unit of Measure: participants
57 46
5.Secondary Outcome
Title Fasting Plasma Glucose (FPG)
Hide Description [Not Specified]
Time Frame During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)]
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmol/L
GW 8-12 IDet (N)=130, NPH (N)=141 5.0  (2.3) 5.8  (3.0)
GW 14 IDet (N)=125, NPH (N)=135 5.0  (3.0) 5.7  (2.7)
GW 24 IDet (N)=129, NPH (N)=141 5.2  (2.4) 6.3  (3.3)
GW 36 IDet (N)=129, NPH (N)=142 4.7  (1.9) 5.4  (2.3)
6.Secondary Outcome
Title 8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24
Hide Description 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.
Time Frame Visit P3 (GW 24)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmol/L
Before Breakfast (N=131,141) 6.4  (1.9) 7.3  (2.0)
120 mins after breakfast (N=130,141) 7.7  (2.3) 8.0  (2.2)
Before Lunch (N=131,141) 6.1  (1.9) 6.7  (2.1)
120 mins after lunch (N=130,140) 7.2  (1.9) 7.4  (2.1)
Before Dinner (N=130,140) 6.8  (2.0) 7.0  (2.1)
120 mins after Dinner (N=117,133) 7.2  (2.0) 7.8  (2.1)
Bedtime (N=125,137) 7.6  (2.4) 7.8  (2.2)
At 2.00 A.M. (N=125,134) 6.7  (2.1) 6.9  (2.3)
7.Secondary Outcome
Title 8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36
Hide Description 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.
Time Frame Visit P4 (GW 36)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmol/L
Before Breakfast (N=131,141) 6  (1.7) 6.3  (1.6)
120 mins after breakfast (N=130,139) 7.4  (2) 7.5  (1.9)
Before Lunch (N=131,141) 5.9  (1.7) 6.1  (1.9)
120 mins after lunch (N=130,140) 6.9  (1.7) 7.1  (2.1)
Before Dinner (N=131,140) 6.5  (1.7) 6.5  (1.9)
120 mins after Dinner (N=117,132) 7.4  (2.1) 7.4  (1.9)
Bedtime (N=126,137) 7  (1.8) 7.2  (2)
At 2.00 A.M. (N=122,135) 6  (1.8) 6.4  (1.8)
8.Secondary Outcome
Title Maternal Safety - Number of Subjects With Adverse Events (AEs)
Hide Description 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.
Time Frame Participants were followed during the pregnancy period, an average of 9.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Measure Type: Number
Unit of Measure: participants
Subjects with (w.) adverse events 138 141
Subjects with serious adverse events 61 49
Subjects with severe adverse events 38 32
Subjects w. AEs related to basal insulin 18 16
Subjects w. AEs related to bolus insulin 12 14
Subjects with AEs leading to withdrawal 13 6
9.Secondary Outcome
Title Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events
Hide Description 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.
Time Frame Foetuses/Newborns were followed during the pregnancy period, an average of 9.6 months and Follow-Up period (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Measure Type: Number
Unit of Measure: Foetus/Newborns (1 per pregnant woman)
Subjects with adverse events 56 55
Subjects with serious adverse events 36 32
Subjects with severe adverse events 15 12
Subjects w. AEs related to Basal insulin 1 0
Subjects w. AEs related to Bolus insulin 1 0
Subjects with AEs leading to withdrawal 0 1
10.Secondary Outcome
Title Maternal Safety - Hypoglycaemic Episodes
Hide Description 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.
Time Frame Participants were followed during the pregnancy period, an average of 9.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 144 146
Measure Type: Number
Unit of Measure: episodes
All Episodes 9496 9453
Diurnal 8045 7810
11.Secondary Outcome
Title Maternal Safety - Nocturnal Hypoglycaemic Episodes
Hide Description 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.
Time Frame Participants were followed during the pregnancy period, an average of 9.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 119 130
Measure Type: Number
Unit of Measure: episodes
1451 1643
12.Secondary Outcome
Title Maternal Safety - Change in Albumin Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: g/dL
Visit P1 IDet (N)=138, NPH (N)=145 4.05  (0.22) 4.04  (0.23)
FU Visit IDet (N)=138, NPH (N)=146 4.19  (0.25) 4.12  (0.27)
Change from Visit P1-FU (N=136, 145) 0.13  (0.26) 0.09  (0.26)
13.Secondary Outcome
Title Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: U/L
Visit P1 IDet (N)=138, NPH (N)=145 16.12  (11.31) 17.97  (9.53)
FU Visit IDet (N)=138, NPH (N)=146 27.06  (14.92) 26.16  (14.21)
Change from Visit P1-FU (N=136, 145) 10.88  (17.51) 8.16  (15.6)
14.Secondary Outcome
Title Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: U/L
Visit P1 IDet (N)=137, NPH (N)=144 52.64  (13.63) 53.88  (13.75)
FU Visit IDet (N)=138, NPH (N)=146 90.17  (26.68) 92.96  (28.07)
Change from Visit P1-FU (N=135, 144) 37.39  (20.86) 39.51  (23.34)
15.Secondary Outcome
Title Maternal Safety - Change in Creatinine Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mcmol/L
Visit P1 IDet (N)=138, NPH (N)=145 52.04  (7.85) 54.01  (8.81)
FU Visit IDet (N)=138, NPH (N)=146 62.98  (9.73) 66.57  (11.8)
Change from Visit P1-FU (N=136, 145) 11.18  (7.61) 12.52  (8.67)
16.Secondary Outcome
Title Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: U/L
Visit P1 IDet (N)=138, NPH (N)=145 145.1  (34.11) 144.1  (24.6)
FU Visit IDet (N)=138, NPH (N)=146 167.5  (29.29) 169.5  (33.75)
Change from Visit P1-FU (N=136, 145) 21.82  (33.61) 25.46  (30.48)
17.Secondary Outcome
Title Maternal Safety - Change in Potassium Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmol/L
Visit P1 IDet (N)=137, NPH (N)=144 4.13  (0.32) 4.12  (0.27)
FU Visit IDet (N)=138, NPH (N)=146 4.30  (0.33) 4.31  (0.34)
Change from Visit P1-FU (N=135, 144) 0.15  (0.36) 0.20  (0.36)
18.Secondary Outcome
Title Maternal Safety - Change in Sodium Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmol/L
Visit P1 IDet (N)=137, NPH (N)=145 138.0  (2.19) 137.8  (2.36)
FU Visit IDet (N)=138, NPH (N)=146 141.6  (2.57) 141.2  (2.71)
Change from Visit P1-FU (N=135, 145) 3.59  (3.19) 3.36  (3.27)
19.Secondary Outcome
Title Maternal Safety - Change in Total Protein Serum Level (Biochemistry)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: g/dL
Visit P1 IDet (N)=138, NPH (N)=145 6.84  (0.37) 6.89  (0.42)
FU Visit IDet (N)=138, NPH (N)=146 7.08  (0.44) 7.11  (0.47)
Change from Visit P1-FU (N=136, 145) 0.24  (0.42) 0.22  (0.39)
20.Secondary Outcome
Title Maternal Safety - Change in Haemoglobin Level (Haematology)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmol/L
Visit P1 IDet (N)=138, NPH (N)=146 7.64  (0.48) 7.64  (0.5)
FU Visit IDet (N)=138, NPH (N)=146 7.81  (0.57) 7.69  (0.57)
Change from Visit P1-FU (N=136, 145) 0.16  (0.57) 0.05  (0.6)
21.Secondary Outcome
Title Maternal Safety - Change in Leukocytes Level (Haematology)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: 10^9 cells/L
Visit P1 IDet (N)=138, NPH (N)=146 8.01  (2.21) 8.2  (2.04)
FU Visit IDet (N)=138, NPH (N)=146 6.68  (1.79) 6.55  (1.92)
Change from Visit P1-FU (N=136, 145) -1.36  (1.93) -1.65  (2.12)
22.Secondary Outcome
Title Maternal Safety - Change in Thrombocytes Level (Haematology)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: 10^9 cells/L
Visit P1 IDet (N)=138, NPH (N)=146 245.3  (48.27) 247.2  (59.32)
FU Visit IDet (N)=138, NPH (N)=146 270.6  (66.01) 263.1  (68.12)
Change from Visit P1-FU (N=136, 145) 24.25  (55.07) 16.16  (52.02)
23.Secondary Outcome
Title Maternal Safety - Change in Urine Albumin Level (Urinalysis)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: g/dL
Visit P1 IDet (N)=135, NPH (N)=143 0.01  (0.02) 0.01  (0.02)
FU Visit IDet (N)=138, NPH (N)=146 0.02  (0.04) 0.03  (0.12)
Change from Visit P1-FU (N=133, 142) 0.01  (0.04) 0.02  (0.11)
24.Secondary Outcome
Title Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mg/mmol
Visit P1 IDet (N)=135, NPH (N)=143 0.82  (1.4) 0.85  (1.65)
FU Visit IDet (N)=138, NPH (N)=146 2.65  (5.6) 4.81  (32.22)
Change from Visit P1-FU (N=133, 142) 1.88  (5.29) 4.07  (32.43)
25.Secondary Outcome
Title Maternal Safety - Change in Urine N (Creatinine) (Urinalysis)
Hide Description 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).
Time Frame Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mg/dL
Visit P1 IDet (N)=135, NPH (N)=144 114.8  (63.77) 103.1  (56.37)
FU Visit IDet (N)=138, NPH (N)=146 106.2  (66.44) 98.61  (58.71)
Change from Visit P1-FU (N=133, 143) -6.62  (83.83) -6.34  (70.79)
26.Secondary Outcome
Title Maternal Safety - Change in Insulin Detemir Specific Antibodies
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Median (Full Range)
Unit of Measure: %B/T
Baseline IDet (N)=145, NPH (N)=155
1.13
(-0.10 to 6.55)
1.09
(-1.36 to 7.35)
Visit P4 IDet (N)=110, NPH (N)=110
1.36
(-0.64 to 12.71)
1.25
(-3.64 to 6.74)
Change from Baseline-Visit P4(N=105,109)
0.04
(-3.89 to 12.11)
0.09
(-5.93 to 6.26)
27.Secondary Outcome
Title Maternal Safety - Change in Insulin Aspart Specific Antibodies
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Median (Full Range)
Unit of Measure: %B/T
Baseline IDet (N)=145, NPH (N)=154
0.44
(-0.25 to 29.74)
0.46
(-0.39 to 55.73)
Visit P4 IDet (N)=109, NPH (N)=110
0.43
(-0.58 to 22.34)
0.36
(-0.52 to 52.23)
Change from Baseline-Visit P4(N=104,109)
-0.12
(-8.63 to 10.10)
-0.21
(-11.6 to 2.11)
28.Secondary Outcome
Title Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies
Hide Description 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
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Median (Full Range)
Unit of Measure: %B/T
Baseline IDet (N)=146, NPH (N)=155
5.21
(-0.02 to 76.75)
5.36
(-0.50 to 67.4)
Visit P4 IDet (N)=110, NPH (N)=110
5.40
(-0.21 to 50.37)
4.28
(-0.22 to 62.25)
Change from Baseline-Visit P4(N=106,109)
-0.43
(-43.3 to 39.43)
-1.12
(-27.9 to 14.52)
29.Secondary Outcome
Title Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood
Hide Description Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).
Time Frame At Delivery (End of Pregnancy)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 104 118
Median (Full Range)
Unit of Measure: %B/T
1.31
(-0.43 to 13.74)
0.90
(-2.48 to 3.23)
30.Secondary Outcome
Title Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood
Hide Description Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T)
Time Frame At Delivery (End of Pregnancy)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 103 118
Median (Full Range)
Unit of Measure: %B/T
0.38
(-0.87 to 19.27)
0.32
(-0.45 to 11.08)
31.Secondary Outcome
Title Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood
Hide Description Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).
Time Frame At Delivery (End of Pregnancy)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 104 119
Median (Full Range)
Unit of Measure: %B/T
5.99
(0.06 to 49.67)
4.12
(0.05 to 74.59)
32.Secondary Outcome
Title Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies
Hide Description Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)
Time Frame At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 94 96
Median (Full Range)
Unit of Measure: ratio
1.10
(-39.2 to 8.80)
0.77
(-4.20 to 7.50)
33.Secondary Outcome
Title Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood
Hide Description [Not Specified]
Time Frame At Delivery
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 98 0
Median (Full Range)
Unit of Measure: pmol/L
25.00
(25.00 to 209.6)
34.Secondary Outcome
Title Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit
Hide Description Change in the body weight was summarised by treatment.
Time Frame Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: kg
GW (8-12) IDet(N)=139,NPH(N)=145 67.8  (11.6) 69.2  (12.5)
Change from GW(8-12)-GW 14 (N=128,139) 1.0  (1.6) 1.4  (1.9)
Change from GW(8-12)-GW 24 (N=130,139) 5.6  (2.7) 6.0  (3.2)
Change from GW(8-12)-GW 36(N=130,139) 11.5  (4.2) 11.0  (5.2)
35.Secondary Outcome
Title Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit
Hide Description Change in the systolic blood pressure was summarised by treatment.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmHg
GW (8-12) IDet(N)=140,NPH(N)=146 114.1  (11.4) 116.2  (10.4)
Change from GW(8-12)-GW 14 (N=137,145) 0.8  (10.1) -2.8  (9.6)
Change from GW(8-12)-GW 24(N=138,145) -0.7  (9.6) -1.6  (11.3)
Change from GW(8-12)-GW 36(N=138,145) 3.1  (11.3) 2.3  (11.8)
Change from GW(8-12)-FU(N=138,145) 2.6  (11.6) -0  (12.5)
36.Secondary Outcome
Title Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit
Hide Description Change in the diastolic blood pressure was summarised by treatment.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: mmHg
GW (8-12) IDet(N)=140,NPH(N)=146 70.5  (8.9) 70.7  (8.2)
Change from GW(8-12)-GW 14 (N=137,145) -0.2  (8.4) -0.5  (9.1)
Change from GW(8-12)-GW 24(N=138,145) -1.6  (8.7) -1.2  (9.3)
Change from GW(8-12)-GW 36(N=138,145) 3.2  (9.9) 2.6  (11.0)
Change from GW(8-12)-FU(N=138,145) 1.3  (9.5) 1.8  (9.8)
37.Secondary Outcome
Title Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up
Hide Description Change in the pulse was summarised by treatment.
Time Frame Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up Visit (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: beats/minute
GW (8-12) IDet(N)=136,NPH(N)=142 77.4  (10) 76.8  (9.6)
Change from GW(8-12)-GW 14 (N=133,139) 1.5  (9.3) 2.2  (10)
Change from GW(8-12)-GW 24(N=134,141) 3.5  (10.6) 4.5  (10.6)
Change from GW(8-12)-GW 36(N=134,141) 5.2  (11.8) 4.9  (12)
Change from GW(8-12)-FU(N=134,141) -3  (11.7) -2.3  (11.9)
38.Secondary Outcome
Title Maternal Safety - Electrocardiogram (ECG)
Hide Description 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.
Time Frame Follow-Up (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Measure Type: Number
Unit of Measure: participants
0 0
39.Secondary Outcome
Title Maternal Safety - Acceleration of Retinopathy in Any Eye
Hide Description 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.
Time Frame From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Measure Type: Number
Unit of Measure: participants
Acceleration in Any Eye 12 14
No Acceleration in Any Eye 120 120
Missing Data 20 24
40.Secondary Outcome
Title Maternal Safety - Acceleration of Nephropathy
Hide Description 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.
Time Frame From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Measure Type: Number
Unit of Measure: participants
2 1
41.Secondary Outcome
Title Maternal Safety - Mode of Delivery
Hide Description Non-Planned Caesarean Section is a procedure which takes place ≤8h prior to delivery. Planned Caesarean Section takes place >8h prior to delivery.
Time Frame At Delivery Visit
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 130 136
Measure Type: Number
Unit of Measure: percentage (%) of subjects
Spontaneous onset of labour (N)=130,136 19 28
Induction of labour (N)=130,136 39 36
Normal Vaginal Delivery(N)=54,50 76 80
Instrumental Vaginal Delivery(N)=54,50 24 20
Non-Planned Caesarean Section(N)=76,86 36 43
Planned Caesarean Section(N)=76,86 65 57
42.Secondary Outcome
Title Pregnancy Outcome at Delivery
Hide Description 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.
Time Frame Delivery Visit
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 142 145
Measure Type: Number
Unit of Measure: participants
Live Birth 128 136
Early Foetal Death (Spont. Abortion) 10 8
Early Foetal Death (Ectopic Pregnancy) 1 1
Induced Abortion 1 0
Stillbirth 2 0
43.Secondary Outcome
Title Pregnancy Outcome at Follow-Up
Hide Description 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.
Time Frame Follow-Up (6 weeks after delivery)
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Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 142 145
Measure Type: Number
Unit of Measure: participants
Live Children 128 135
Early Foetal Death (Spont. Abortion) 10 8
Early Foetal Death (Ectopic Pregnancy) 1 1
Induced Abortion 1 0
Perinatal Death 2 1
Neonatal Death 0 0
Death During Follow-Up 0 0
44.Secondary Outcome
Title Safety - Total Daily Insulin Dose During Pregnancy
Hide Description [Not Specified]
Time Frame Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Mean (Standard Deviation)
Unit of Measure: U/kg
GW 14 IDet (N)=129, NPH (N)=141 0.73  (0.23) 0.74  (0.25)
GW 24 IDet (N)=128, NPH (N)=137 0.85  (0.29) 0.84  (0.26)
GW 36 IDet (N)=119, NPH (N)=121 1.17  (0.47) 1.05  (0.35)
Follow-Up IDet (N)=124, NPH (N)=133 0.53  (0.17) 0.57  (0.2)
45.Secondary Outcome
Title Safety - Composite Pregnancy Outcome
Hide Description 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.
Time Frame End of Pregnancy
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 152 158
Measure Type: Number
Unit of Measure: participants
Wt. below the 10th percentile(N)=128,136 3 1
Wt. above the 90th percentile(N)=128,136 59 73
Pre-term delivery (N)=142,145 39 45
Major malformations (N)=142,145 5 1
Early foetal death (N)=142,145 11 9
Perinatal mortality (N)=130,136 2 1
Neonatal mortality (N)=126,135 0 0
Compiled(at least 1 of above)(N)=142,145 89 96
46.Secondary Outcome
Title Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies
Hide Description Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)
Time Frame At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 93 95
Median (Full Range)
Unit of Measure: ratio
0.84
(-2.85 to 8.0)
0.64
(-25.5 to 5.0)
47.Secondary Outcome
Title Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies
Hide Description Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)
Time Frame At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description:
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
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 Number of Participants Analyzed 94 98
Median (Full Range)
Unit of Measure: ratio
1.29
(-76.0 to 8.83)
0.90
(-3.86 to 57.82)
Time Frame Maternal AEs were collected and reported during the entire pregnancy period, an average of 9.6 months
Adverse Event Reporting Description 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.
 
Arm/Group Title Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Hide Arm/Group Description 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 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
All-Cause Mortality
Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   61/152 (40.13%)      49/158 (31.01%)    
Blood and lymphatic system disorders     
Abortion threatened  1 [1]  3/152 (1.97%)  3 0/158 (0.00%)  0
Antepartum haemorrhage  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Placental insufficiency  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Eye disorders     
Retinopathy  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Visual impairment  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Gastrointestinal disorders     
Vomiting  1 [1]  5/152 (3.29%)  5 2/158 (1.27%)  2
Nausea  1 [1]  2/152 (1.32%)  3 2/158 (1.27%)  2
Abdominal pain, upper  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  2
Diarrhoea  1 [1]  1/152 (0.66%)  1 1/158 (0.63%)  1
Abdominal pain  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Impaired gastric emptying  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
General disorders     
Device failure  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Malaise  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Hepatobiliary disorders     
Cholestasis of pregnancy  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Cytolytic hepatitis  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Infections and infestations     
Gastroenteritis  1 [1]  4/152 (2.63%)  4 1/158 (0.63%)  1
Beta haemolytic streptococcal infection  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Pyelonephritis  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Urinary tract infection  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Urogenital infection bacterial  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Injury, poisoning and procedural complications     
Incorrect dose administered  1 [1]  0/152 (0.00%)  0 2/158 (1.27%)  2
Wrong drug administered  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Investigations     
Amniotic fluid volume decreased  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Metabolism and nutrition disorders     
Hypoglycaemia  1 [1]  5/152 (3.29%)  5 5/158 (3.16%)  12
Hypoglycaemic unconsciousness  1 [1]  2/152 (1.32%)  4 7/158 (4.43%)  9
Diabetes mellitus inadequate control  1 [1]  5/152 (3.29%)  5 1/158 (0.63%)  1
Diabetic ketoacidosis  1 [1]  3/152 (1.97%)  3 0/158 (0.00%)  0
Hyperglycaemia  1 [1]  2/152 (1.32%)  2 0/158 (0.00%)  0
Nervous system disorders     
Headache  1 [1]  3/152 (1.97%)  3 2/158 (1.27%)  2
Migraine  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Aborption spontaneous  1 [1]  8/152 (5.26%)  8 4/158 (2.53%)  4
Pre-eclampsia  1 [1]  8/152 (5.26%)  8 1/158 (0.63%)  1
Threatened labour  1 [1]  3/152 (1.97%)  3 4/158 (2.53%)  4
Failed induction of labour  1 [1]  3/152 (1.97%)  3 3/158 (1.90%)  3
Abortion missed  1 [1]  1/152 (0.66%)  1 2/158 (1.27%)  2
Hyperemesis gravidarum  1 [1]  1/152 (0.66%)  1 2/158 (1.27%)  2
Ectopic pregnancy  1 [1]  1/152 (0.66%)  1 1/158 (0.63%)  1
Gestational hypertension  1 [1]  1/152 (0.66%)  1 1/158 (0.63%)  1
Intra-uterine death  1 [1]  1/152 (0.66%)  1 1/158 (0.63%)  1
Placenta praevia  1 [1]  0/152 (0.00%)  0 2/158 (1.27%)  2
Placenta praevia haemorrhage  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  2
Premature labour  1 [1]  2/152 (1.32%)  2 0/158 (0.00%)  0
Premature separation of placenta  1 [1]  0/152 (0.00%)  0 2/158 (1.27%)  2
Aborption incomplete  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Blighted ovum  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Breech presentation  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Cephalo-pelvic disproportion  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Cervical incompetence  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Imminent abortion  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Labour complication  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Polyhydramnios  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Premature rupture of membranes  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Stillbirth  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Uterine contractions abnormal  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Reproductive system and breast disorders     
Uterine haemorrhage  1 [1]  1/152 (0.66%)  1 2/158 (1.27%)  2
Metrorrhagia  1 [1]  1/152 (0.66%)  1 1/158 (0.63%)  1
Genital haemorrhage  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Pelvic pain  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Vaginal haematoma  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Skin and subcutaneous tissue disorders     
Polymorphic eruption of pregnancy  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Social circumstances     
Inadequate diet  1 [1]  1/152 (0.66%)  1 0/158 (0.00%)  0
Social stay hospitalisation  1 [1]  0/152 (0.00%)  0 1/158 (0.63%)  1
Vascular disorders     
Hypertension  1 [1]  2/152 (1.32%)  3 1/158 (0.63%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
[1]
SAE for Mother, Safety-Pregnant
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Insulin Detemir Neutral Protamine Hagedorn (NPH) Insulin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   138/152 (90.79%)      141/158 (89.24%)    
Blood and lymphatic system disorders     
Anaemia  1 [1]  22/152 (14.47%)  23 23/158 (14.56%)  24
Eye disorders     
Diabetic Retinopathy  1 [1]  6/152 (3.95%)  6 10/158 (6.33%)  13
Gastrointestinal disorders     
Diarrhoea  1 [1]  21/152 (13.82%)  27 11/158 (6.96%)  13
Abdominal Pain  1 [1]  11/152 (7.24%)  15 12/158 (7.59%)  22
Abdominal pain upper  1 [1]  12/152 (7.89%)  14 5/158 (3.16%)  7
Toothache  1 [1]  7/152 (4.61%)  9 9/158 (5.70%)  12
Constipation  1 [1]  4/152 (2.63%)  4 11/158 (6.96%)  11
Infections and infestations     
Nasopharyngitis  1 [1]  45/152 (29.61%)  82 47/158 (29.75%)  68
Urinary Tract Infection  2 [1]  17/152 (11.18%)  19 12/158 (7.59%)  14
Gastroenteritis  1 [1]  13/152 (8.55%)  13 9/158 (5.70%)  11
Upper respiratory tract infection  1 [1]  9/152 (5.92%)  10 13/158 (8.23%)  17
Influenza  1 [1]  9/152 (5.92%)  12 16/158 (10.13%)  16
Nervous system disorders     
Headache  1 [1]  43/152 (28.29%)  109 35/158 (22.15%)  121
Pregnancy, puerperium and perinatal conditions     
Pre-eclampsia  1 [1]  8/152 (5.26%)  8 10/158 (6.33%)  10
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1 [1]  11/152 (7.24%)  13 13/158 (8.23%)  17
Vascular disorders     
Hypertension  1 [1]  5/152 (3.29%)  5 8/158 (5.06%)  8
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
2
Term from vocabulary, MedDRA
[1]
AE for Mother, Safety-Pregnant
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00474045    
Other Study ID Numbers: NN304-1687
2006-004861-33 ( EudraCT Number )
First Submitted: May 15, 2007
First Posted: May 16, 2007
Results First Submitted: August 5, 2011
Results First Posted: December 5, 2011
Last Update Posted: March 10, 2017