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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00474045
• Collaborator: (none)
• Enrollment: 470
• Locations: 100
• Arms: 2
• Duration (Months): 39
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial is conducted in Africa, Europe, North and South America and Oceania. The aim of this trial is to compare the effect and safety on blood glucose control in pregnant women with type 1 diabetes of a modern insulin analogue (insulin detemir) and human insulin (NPH insulin) given as long-acting insulin in combination with a short-acting insulin (insulin aspart).

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 1	Drug: insulin detemir; Drug: NPH insulin; Drug: insulin aspart	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 470 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Parallel-group, Open-labelled, Multinational Trial Comparing the Efficacy and Safety of Insulin Detemir (Levemir®) Versus Human Insulin (NPH Insulin), Used in Combination With Insulin Aspart as Bolus Insulin, in the Treatment of Pregnant Women With Type 1 Diabetes
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin detemir Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Drug: insulin detemir; Treat-to-target, dose titration, s.c. (under the skin) injection; Drug: insulin aspart; Treat-to-target, dose titration, s.c. (under the skin) injection
Active Comparator: Neutral Protamine Hagedorn (NPH) insulin Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Drug: NPH insulin; Treat-to-target, dose titration, s.c. (under the skin) injection; Drug: insulin aspart; Treat-to-target, dose titration, s.c. (under the skin) injection

Outcome Measures

Primary Outcome Measures

1. Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36 [At gestational week (GW) 36]

2. Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36 [At gestational week (GW) 36]

Secondary Outcome Measures

1. Glycosylated Haemoglobin (HbA1c) During Pregnancy [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)]

2. Subjects Reaching HbA1c at or Below 6.0% Both at GW 24 and GW 36 [At both Visit P3 (GW 24) and Visit P4 (GW 36)]

3. Fasting Plasma Glucose (FPG) [During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)]]

4. 8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 [Visit P3 (GW 24)]

   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.

5. 8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 [Visit P4 (GW 36)]

   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.

6. Maternal Safety - Number of Subjects With Adverse Events (AEs) [Participants were followed during the pregnancy period, an average of 9.6 months]

   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.

7. Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events [Foetuses/Newborns were followed during the pregnancy period, an average of 9.6 months and Follow-Up period (6 weeks after delivery)]

   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.

8. Maternal Safety - Hypoglycaemic Episodes [Participants were followed during the pregnancy period, an average of 9.6 months]

   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.

9. Maternal Safety - Nocturnal Hypoglycaemic Episodes [Participants were followed during the pregnancy period, an average of 9.6 months]

   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.

10. Maternal Safety - Change in Albumin Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

11. Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

12. Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

13. Maternal Safety - Change in Creatinine Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

14. Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

15. Maternal Safety - Change in Potassium Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

16. Maternal Safety - Change in Sodium Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

17. Maternal Safety - Change in Total Protein Serum Level (Biochemistry) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

18. Maternal Safety - Change in Haemoglobin Level (Haematology) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

19. Maternal Safety - Change in Leukocytes Level (Haematology) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

20. Maternal Safety - Change in Thrombocytes Level (Haematology) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

21. Maternal Safety - Change in Urine Albumin Level (Urinalysis) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

22. Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

23. Maternal Safety - Change in Urine N (Creatinine) (Urinalysis) [Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)]

    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).

24. Maternal Safety - Change in Insulin Detemir Specific Antibodies [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.]

    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.

25. Maternal Safety - Change in Insulin Aspart Specific Antibodies [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.]

    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.

26. Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies [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.]

    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

27. Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood [At Delivery (End of Pregnancy)]

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

28. Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood [At Delivery (End of Pregnancy)]

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

29. Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood [At Delivery (End of Pregnancy)]

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

30. Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies [At Delivery (End of Pregnancy) and at Visit P4 (GW 36)]

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

31. Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood [At Delivery]

32. Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit [Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)]

    Change in the body weight was summarised by treatment.

33. Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit [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)]

    Change in the systolic blood pressure was summarised by treatment.

34. Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit [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)]

    Change in the diastolic blood pressure was summarised by treatment.

35. Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up [Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up Visit (6 weeks after delivery)]

    Change in the pulse was summarised by treatment.

36. Maternal Safety - Electrocardiogram (ECG) [Follow-Up (6 weeks after delivery)]

    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.

37. Maternal Safety - Acceleration of Retinopathy in Any Eye [From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)]

    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.

38. Maternal Safety - Acceleration of Nephropathy [From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)]

    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.

39. Maternal Safety - Mode of Delivery [At Delivery Visit]

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

40. Pregnancy Outcome at Delivery [Delivery Visit]

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

41. Pregnancy Outcome at Follow-Up [Follow-Up (6 weeks after delivery)]

    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.

42. Safety - Total Daily Insulin Dose During Pregnancy [Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery)]

43. Safety - Composite Pregnancy Outcome [End of Pregnancy]

    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.

44. Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies [At Delivery (End of Pregnancy) and at Visit P4 (GW 36)]

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

45. Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies [At Delivery (End of Pregnancy) and at Visit P4 (GW 36)]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 1 diabetes treated with insulin for at least 12 months

• Planning to become pregnant and have a screening HbA1c (glycosylated haemoglobin) lesser than or equal to 9.0%, or

• Pregnant with an intrauterine singleton living foetus, 8-12 weeks pregnant when joining the trial and a HbA1c lesser than or equal to 8.0% when pregnancy is confirmed

Exclusion Criteria:

• Known or suspected hypersensitivity to the trial product(s) or related products

• Untreated hyperthyroidism or hypothyroidism

• Known or suspected abuse of alcohol or narcotics

• Cardiac problems

• Impaired kidney function

• History of severe hyperemesis gravidarum

• Treatment with in-vitro fertilisation or other medical infertility treatment

• Impaired liver function

• Uncontrolled hypertension

• Proliferative retinopathy or maculopathy requiring acute treatment

• Known to be HIV (human immunodeficiency virus) positive, Hepatitis B or Hepatitis C positive

• Any concomitant medication contraindicated in pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Buenos Aires		Argentina	B1704ETD
2	Novo Nordisk Investigational Site	Buenos Aires		Argentina	C1155ADP
3	Novo Nordisk Investigational Site	Buenos Aires		Argentina	C1181ACH
4	Novo Nordisk Investigational Site	Buenos Aires		Argentina	C1246ABQ
5	Novo Nordisk Investigational Site	Mar del Plata		Argentina	B7602CBM
6	Novo Nordisk Investigational Site	Pcia de Cordoba		Argentina	5000
7	Novo Nordisk Investigational Site	Salta		Argentina	A4406CLA
8	Novo Nordisk Investigational Site	Broadmeadow	New South Wales	Australia	2292
9	Novo Nordisk Investigational Site	Camperdown	New South Wales	Australia	2050
10	Novo Nordisk Investigational Site	St Leonards	New South Wales	Australia	2065
11	Novo Nordisk Investigational Site	Elizabeth Vale	South Australia	Australia	5112
12	Novo Nordisk Investigational Site	Clayton		Australia	3168
13	Novo Nordisk Investigational Site	Garran		Australia	2605
14	Novo Nordisk Investigational Site	South Brisbane		Australia	4101
15	Novo Nordisk Investigational Site	Subiaco		Australia	6008
16	Novo Nordisk Investigational Site	Wollongong		Australia	2500
17	Novo Nordisk Investigational Site	Feldkirch		Austria	6807
18	Novo Nordisk Investigational Site	Innsbruck		Austria	6020
19	Novo Nordisk Investigational Site	Salzburg		Austria	5020
20	Novo Nordisk Investigational Site	Wien		Austria	1030
21	Novo Nordisk Investigational Site	Wien		Austria	1090
22	Novo Nordisk Investigational Site	Wien		Austria	1130
23	Novo Nordisk Investigational Site	Wien		Austria	1170
24	Novo Nordisk Investigational Site	Curitiba	Parana	Brazil	80030-110
25	Novo Nordisk Investigational Site	Porto Alegre		Brazil	90035-170
26	Novo Nordisk Investigational Site	Sao Paulo		Brazil	01221-900
27	Novo Nordisk Investigational Site	São Paulo		Brazil	04022-002
28	Novo Nordisk Investigational Site	Calgary	Alberta	Canada	T2H 2G4
29	Novo Nordisk Investigational Site	Cambridge	Ontario	Canada	N1R 7L6
30	Novo Nordisk Investigational Site	London	Ontario	Canada	N6A 4V2
31	Novo Nordisk Investigational Site	Edmonton		Canada	T6G 2S2
32	Novo Nordisk Investigational Site	Montreal		Canada	H3A 1A1
33	Novo Nordisk Investigational Site	Quebec		Canada	G1V 4G2
34	Novo Nordisk Investigational Site	Toronto		Canada	M5G 1X5
35	Novo Nordisk Investigational Site	Toronto		Canada	M5S 1B2
36	Novo Nordisk Investigational Site	Vancouver		Canada	V6H 3N1
37	Novo Nordisk Investigational Site	Winnipeg		Canada	R3C 0N2
38	Novo Nordisk Investigational Site	Zagreb		Croatia	10 000
39	Novo Nordisk Investigational Site	Aalborg		Denmark	9000
40	Novo Nordisk Investigational Site	Aarhus N		Denmark	8200
41	Novo Nordisk Investigational Site	København ø		Denmark	2100
42	Novo Nordisk Investigational Site	Helsinki		Finland	00029
43	Novo Nordisk Investigational Site	Amiens		France
44	Novo Nordisk Investigational Site	Angers		France	49000
45	Novo Nordisk Investigational Site	Bondy		France	93143
46	Novo Nordisk Investigational Site	Lille		France	59037
47	Novo Nordisk Investigational Site	Marseille		France	13009
48	Novo Nordisk Investigational Site	MONTPELLIER cedex 5		France	34295
49	Novo Nordisk Investigational Site	Nimes		France	30006
50	Novo Nordisk Investigational Site	Strasbourg		France	67000
51	Novo Nordisk Investigational Site	TOULOUSE cedex 9		France	31059
52	Novo Nordisk Investigational Site	Valenciennes		France	59322
53	Novo Nordisk Investigational Site	Dublin 1		Ireland
54	Novo Nordisk Investigational Site	Dublin 2		Ireland
55	Novo Nordisk Investigational Site	Dublin 8		Ireland
56	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 7
57	Novo Nordisk Investigational Site	Petach Tikva		Israel	49100
58	Novo Nordisk Investigational Site	Bergen		Norway	5021
59	Novo Nordisk Investigational Site	Trondheim		Norway	NO-7030
60	Novo Nordisk Investigational Site	Tønsberg		Norway	3116
61	Novo Nordisk Investigational Site	Krakow		Poland	31-501
62	Novo Nordisk Investigational Site	Lodz		Poland	93-338
63	Novo Nordisk Investigational Site	Lublin		Poland	20-081
64	Novo Nordisk Investigational Site	Olsztyn		Poland	10-061
65	Novo Nordisk Investigational Site	Szczecin		Poland	71-455
66	Novo Nordisk Investigational Site	Warszawa		Poland	02-097
67	Novo Nordisk Investigational Site	Warszawa		Poland	03-242
68	Novo Nordisk Investigational Site	Wroclaw		Poland	50-306
69	Novo Nordisk Investigational Site	Zabrze		Poland	41-800
70	Novo Nordisk Investigational Site	Moscow		Russian Federation	101000
71	Novo Nordisk Investigational Site	Moscow		Russian Federation	127411
72	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630047
73	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	199034
74	Novo Nordisk Investigational Site	Samara		Russian Federation	443095
75	Novo Nordisk Investigational Site	Tumen		Russian Federation	625023
76	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6014
77	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6045
78	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0001
79	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4001
80	Novo Nordisk Investigational Site	Alcoy		Spain	03803
81	Novo Nordisk Investigational Site	Alicante		Spain	03010
82	Novo Nordisk Investigational Site	Barcelona		Spain	08025
83	Novo Nordisk Investigational Site	Madrid		Spain	28009
84	Novo Nordisk Investigational Site	Santander		Spain	39008
85	Novo Nordisk Investigational Site	Sevilla		Spain	41014
86	Novo Nordisk Investigational Site	Valencia		Spain	46017
87	Novo Nordisk Investigational Site	Belfast		United Kingdom	BT12 6BA
88	Novo Nordisk Investigational Site	Birmingham		United Kingdom	B9 5SS
89	Novo Nordisk Investigational Site	Blackburn		United Kingdom	BB2 3HH
90	Novo Nordisk Investigational Site	Bristol		United Kingdom	BS10 5NB
91	Novo Nordisk Investigational Site	Edinburgh		United Kingdom	EH16 4SA
92	Novo Nordisk Investigational Site	Exeter		United Kingdom	EX2 5AX
93	Novo Nordisk Investigational Site	Leicester		United Kingdom	LE1 5WW
94	Novo Nordisk Investigational Site	London		United Kingdom	W12 0NN
95	Novo Nordisk Investigational Site	Middlesbrough		United Kingdom	TS4 3BW
96	Novo Nordisk Investigational Site	Northampton		United Kingdom	NN1 5BD
97	Novo Nordisk Investigational Site	Norwich		United Kingdom	NR4 7UY
98	Novo Nordisk Investigational Site	Plymouth		United Kingdom	PL6 8BQ
99	Novo Nordisk Investigational Site	Southampton		United Kingdom	SO16 5YA
100	Novo Nordisk Investigational Site	Watford		United Kingdom	WD18 0HB

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00474045
• Other Study ID Numbers: NN304-1687; 2006-004861-33
• First Posted: May 16, 2007
• Last Update Posted: Mar 10, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef

Study Results

Participant Flow

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 Detail	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
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
Exposed-Pregnant Subjects	152	158
Pregnancies (for Exposed-pregnant)	152	160
COMPLETED	127	136
NOT COMPLETED	106	101

Baseline Characteristics

Arm/Group Title	Insulin Detemir	Neutral Protamine Hagedorn (NPH) Insulin	Total
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 Participants	152	158	310
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.7 (4.62)	30.4 (4.21)	30.1 (4.43)
Sex: Female, Male (Count of Participants)
Female	152 100%	158 100%	310 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%	1 0.6%	1 0.3%
Asian	1 0.7%	3 1.9%	4 1.3%
Black or African American	1 0.7%	0 0%	1 0.3%
White	135 88.8%	142 89.9%	277 89.4%
Unknown	12 7.9%	10 6.3%	22 7.1%
Other	3 2%	2 1.3%	5 1.6%
Height (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	1.67 (0.07)	1.65 (0.06)	1.66 (0.07)
Body Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	67.6 (12.3)	68.7 (12.4)	68.2 (12.3)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.34 (3.95)	25.17 (4.22)	24.76 (4.1)
Smoker (participants) [Number]
No	143 94.1%	147 93%	290 93.5%
Yes	9 5.9%	11 7%	20 6.5%
Daily Use of Alcohol (participants) [Number]
No	150 98.7%	158 100%	308 99.4%
Yes	2 1.3%	0 0%	2 0.6%
Stratification (participants) [Number]
Pregnant after Randomisation	73 48%	75 47.5%	148 47.7%
Pregnant at Randomisation	79 52%	83 52.5%	162 52.3%
Glycosylated Haemoglobin (HbA1c) (Percent (%) glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent (%) glycosylated haemoglobin]	6.95 (0.82)	7.08 (0.76)	7.01 (0.79)
Fasting Plasma Glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.89 (3.29)	5.99 (3.23)	5.94 (3.25)
Diabetes History (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.72 (8.08)	12.78 (7.94)	12.26 (8.02)

Outcome Measures

1. Primary Outcome

Title	Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36
Time Frame	At gestational week (GW) 36

Outcome Measure Data

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
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
Measure Participants	138	145
Least Squares Mean (Standard Error) [Percent (%) glycosylated haemoglobin]	6.27 (0.053)	6.33 (0.052)

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
Time Frame	At gestational week (GW) 36

Outcome Measure Data

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
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
Measure Participants	127	135
Least Squares Mean (Standard Error) [Percent (%) glycosylated haemoglobin]	6.22 (0.069)	6.37 (0.067)

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
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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
Time Frame	At both Visit P3 (GW 24) and Visit P4 (GW 36)

Outcome Measure Data

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
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
Measure Participants	138	146
Number [participants]	57 37.5%	46 29.1%

5. Secondary Outcome

Title	Fasting Plasma Glucose (FPG)
Time Frame	During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)]

Outcome Measure Data

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
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
Measure Participants	152	158
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
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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

Outcome Measure Data

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
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
Measure Participants	152	158
Subjects with (w.) adverse events	138 90.8%	141 89.2%
Subjects with serious adverse events	61 40.1%	49 31%
Subjects with severe adverse events	38 25%	32 20.3%
Subjects w. AEs related to basal insulin	18 11.8%	16 10.1%
Subjects w. AEs related to bolus insulin	12 7.9%	14 8.9%
Subjects with AEs leading to withdrawal	13 8.6%	6 3.8%

9. Secondary Outcome

Title	Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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
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

Outcome Measure Data

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
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
Measure Participants	144	146
All Episodes	9496	9453
Diurnal	8045	7810

11. Secondary Outcome

Title	Maternal Safety - Nocturnal Hypoglycaemic Episodes
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

Outcome Measure Data

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
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
Measure Participants	119	130
Number [episodes]	1451	1643

12. Secondary Outcome

Title	Maternal Safety - Change in Albumin Serum Level (Biochemistry)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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
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.

Outcome Measure Data

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
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
Measure Participants	152	158
Baseline IDet (N)=145, NPH (N)=155	1.13	1.09
Visit P4 IDet (N)=110, NPH (N)=110	1.36	1.25
Change from Baseline-Visit P4(N=105,109)	0.04	0.09

27. Secondary Outcome

Title	Maternal Safety - Change in Insulin Aspart Specific Antibodies
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.

Outcome Measure Data

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
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
Measure Participants	152	158
Baseline IDet (N)=145, NPH (N)=154	0.44	0.46
Visit P4 IDet (N)=109, NPH (N)=110	0.43	0.36
Change from Baseline-Visit P4(N=104,109)	-0.12	-0.21

28. Secondary Outcome

Title	Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies
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.

Outcome Measure Data

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
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
Measure Participants	152	158
Baseline IDet (N)=146, NPH (N)=155	5.21	5.36
Visit P4 IDet (N)=110, NPH (N)=110	5.40	4.28
Change from Baseline-Visit P4(N=106,109)	-0.43	-1.12

29. Secondary Outcome

Title	Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood
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)

Outcome Measure Data

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
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
Measure Participants	104	118
Median (Full Range) [%B/T]	1.31	0.90

30. Secondary Outcome

Title	Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood
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)

Outcome Measure Data

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
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
Measure Participants	103	118
Median (Full Range) [%B/T]	0.38	0.32

31. Secondary Outcome

Title	Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood
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)

Outcome Measure Data

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
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
Measure Participants	104	119
Median (Full Range) [%B/T]	5.99	4.12

32. Secondary Outcome

Title	Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies
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)

Outcome Measure Data

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
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
Measure Participants	94	96
Median (Full Range) [ratio]	1.10	0.77

33. Secondary Outcome

Title	Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood
Time Frame	At Delivery

Outcome Measure Data

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
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
Measure Participants	98	0
Median (Full Range) [pmol/L]	25.00

34. Secondary Outcome

Title	Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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
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)

Outcome Measure Data

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
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
Measure Participants	152	158
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)
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)

Outcome Measure Data

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
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
Measure Participants	152	158
Number [participants]	0 0%	0 0%

39. Secondary Outcome

Title	Maternal Safety - Acceleration of Retinopathy in Any Eye
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)

Outcome Measure Data

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
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
Measure Participants	152	158
Acceleration in Any Eye	12 7.9%	14 8.9%
No Acceleration in Any Eye	120 78.9%	120 75.9%
Missing Data	20 13.2%	24 15.2%

40. Secondary Outcome

Title	Maternal Safety - Acceleration of Nephropathy
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)

Outcome Measure Data

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
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
Measure Participants	152	158
Number [participants]	2 1.3%	1 0.6%

41. Secondary Outcome

Title	Maternal Safety - Mode of Delivery
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

Outcome Measure Data

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
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
Measure Participants	130	136
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
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

Outcome Measure Data

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
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
Measure Participants	142	145
Live Birth	128 84.2%	136 86.1%
Early Foetal Death (Spont. Abortion)	10 6.6%	8 5.1%
Early Foetal Death (Ectopic Pregnancy)	1 0.7%	1 0.6%
Induced Abortion	1 0.7%	0 0%
Stillbirth	2 1.3%	0 0%

43. Secondary Outcome

Title	Pregnancy Outcome at Follow-Up
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)

Outcome Measure Data

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
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
Measure Participants	142	145
Live Children	128 84.2%	135 85.4%
Early Foetal Death (Spont. Abortion)	10 6.6%	8 5.1%
Early Foetal Death (Ectopic Pregnancy)	1 0.7%	1 0.6%
Induced Abortion	1 0.7%	0 0%
Perinatal Death	2 1.3%	1 0.6%
Neonatal Death	0 0%	0 0%
Death During Follow-Up	0 0%	0 0%

44. Secondary Outcome

Title	Safety - Total Daily Insulin Dose During Pregnancy
Time Frame	Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery)

Outcome Measure Data

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
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
Measure Participants	152	158
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
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

Outcome Measure Data

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
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
Measure Participants	152	158
Wt. below the 10th percentile(N)=128,136	3 2%	1 0.6%
Wt. above the 90th percentile(N)=128,136	59 38.8%	73 46.2%
Pre-term delivery (N)=142,145	39 25.7%	45 28.5%
Major malformations (N)=142,145	5 3.3%	1 0.6%
Early foetal death (N)=142,145	11 7.2%	9 5.7%
Perinatal mortality (N)=130,136	2 1.3%	1 0.6%
Neonatal mortality (N)=126,135	0 0%	0 0%
Compiled(at least 1 of above)(N)=142,145	89 58.6%	96 60.8%

46. Secondary Outcome

Title	Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies
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)

Outcome Measure Data

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
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
Measure Participants	93	95
Median (Full Range) [ratio]	0.84	0.64

47. Secondary Outcome

Title	Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies
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)

Outcome Measure Data

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
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
Measure Participants	94	98
Median (Full Range) [ratio]	1.29	0.90

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Detemir		Neutral Protamine Hagedorn (NPH) Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/152 (40.1%)		49/158 (31%)
Blood and lymphatic system disorders
Abortion threatened	3/152 (2%)	3	0/158 (0%)	0
Antepartum haemorrhage	0/152 (0%)	0	1/158 (0.6%)	1
Placental insufficiency	0/152 (0%)	0	1/158 (0.6%)	1
Eye disorders
Retinopathy	1/152 (0.7%)	1	0/158 (0%)	0
Visual impairment	1/152 (0.7%)	1	0/158 (0%)	0
Gastrointestinal disorders
Vomiting	5/152 (3.3%)	5	2/158 (1.3%)	2
Nausea	2/152 (1.3%)	3	2/158 (1.3%)	2
Abdominal pain, upper	0/152 (0%)	0	1/158 (0.6%)	2
Diarrhoea	1/152 (0.7%)	1	1/158 (0.6%)	1
Abdominal pain	0/152 (0%)	0	1/158 (0.6%)	1
Impaired gastric emptying	1/152 (0.7%)	1	0/158 (0%)	0
General disorders
Device failure	1/152 (0.7%)	1	0/158 (0%)	0
Malaise	1/152 (0.7%)	1	0/158 (0%)	0
Hepatobiliary disorders
Cholestasis of pregnancy	1/152 (0.7%)	1	0/158 (0%)	0
Cytolytic hepatitis	1/152 (0.7%)	1	0/158 (0%)	0
Infections and infestations
Gastroenteritis	4/152 (2.6%)	4	1/158 (0.6%)	1
Beta haemolytic streptococcal infection	0/152 (0%)	0	1/158 (0.6%)	1
Pyelonephritis	1/152 (0.7%)	1	0/158 (0%)	0
Urinary tract infection	1/152 (0.7%)	1	0/158 (0%)	0
Urogenital infection bacterial	1/152 (0.7%)	1	0/158 (0%)	0
Injury, poisoning and procedural complications
Incorrect dose administered	0/152 (0%)	0	2/158 (1.3%)	2
Wrong drug administered	0/152 (0%)	0	1/158 (0.6%)	1
Investigations
Amniotic fluid volume decreased	1/152 (0.7%)	1	0/158 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	5/152 (3.3%)	5	5/158 (3.2%)	12
Hypoglycaemic unconsciousness	2/152 (1.3%)	4	7/158 (4.4%)	9
Diabetes mellitus inadequate control	5/152 (3.3%)	5	1/158 (0.6%)	1
Diabetic ketoacidosis	3/152 (2%)	3	0/158 (0%)	0
Hyperglycaemia	2/152 (1.3%)	2	0/158 (0%)	0
Nervous system disorders
Headache	3/152 (2%)	3	2/158 (1.3%)	2
Migraine	1/152 (0.7%)	1	0/158 (0%)	0
Pregnancy, puerperium and perinatal conditions
Aborption spontaneous	8/152 (5.3%)	8	4/158 (2.5%)	4
Pre-eclampsia	8/152 (5.3%)	8	1/158 (0.6%)	1
Threatened labour	3/152 (2%)	3	4/158 (2.5%)	4
Failed induction of labour	3/152 (2%)	3	3/158 (1.9%)	3
Abortion missed	1/152 (0.7%)	1	2/158 (1.3%)	2
Hyperemesis gravidarum	1/152 (0.7%)	1	2/158 (1.3%)	2
Ectopic pregnancy	1/152 (0.7%)	1	1/158 (0.6%)	1
Gestational hypertension	1/152 (0.7%)	1	1/158 (0.6%)	1
Intra-uterine death	1/152 (0.7%)	1	1/158 (0.6%)	1
Placenta praevia	0/152 (0%)	0	2/158 (1.3%)	2
Placenta praevia haemorrhage	0/152 (0%)	0	1/158 (0.6%)	2
Premature labour	2/152 (1.3%)	2	0/158 (0%)	0
Premature separation of placenta	0/152 (0%)	0	2/158 (1.3%)	2
Aborption incomplete	1/152 (0.7%)	1	0/158 (0%)	0
Blighted ovum	0/152 (0%)	0	1/158 (0.6%)	1
Breech presentation	1/152 (0.7%)	1	0/158 (0%)	0
Cephalo-pelvic disproportion	1/152 (0.7%)	1	0/158 (0%)	0
Cervical incompetence	0/152 (0%)	0	1/158 (0.6%)	1
Imminent abortion	1/152 (0.7%)	1	0/158 (0%)	0
Labour complication	1/152 (0.7%)	1	0/158 (0%)	0
Polyhydramnios	0/152 (0%)	0	1/158 (0.6%)	1
Premature rupture of membranes	0/152 (0%)	0	1/158 (0.6%)	1
Stillbirth	1/152 (0.7%)	1	0/158 (0%)	0
Uterine contractions abnormal	1/152 (0.7%)	1	0/158 (0%)	0
Reproductive system and breast disorders
Uterine haemorrhage	1/152 (0.7%)	1	2/158 (1.3%)	2
Metrorrhagia	1/152 (0.7%)	1	1/158 (0.6%)	1
Genital haemorrhage	1/152 (0.7%)	1	0/158 (0%)	0
Pelvic pain	0/152 (0%)	0	1/158 (0.6%)	1
Vaginal haematoma	0/152 (0%)	0	1/158 (0.6%)	1
Skin and subcutaneous tissue disorders
Polymorphic eruption of pregnancy	0/152 (0%)	0	1/158 (0.6%)	1
Social circumstances
Inadequate diet	1/152 (0.7%)	1	0/158 (0%)	0
Social stay hospitalisation	0/152 (0%)	0	1/158 (0.6%)	1
Vascular disorders
Hypertension	2/152 (1.3%)	3	1/158 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Insulin Detemir		Neutral Protamine Hagedorn (NPH) Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	138/152 (90.8%)		141/158 (89.2%)
Blood and lymphatic system disorders
Anaemia	22/152 (14.5%)	23	23/158 (14.6%)	24
Eye disorders
Diabetic Retinopathy	6/152 (3.9%)	6	10/158 (6.3%)	13
Gastrointestinal disorders
Diarrhoea	21/152 (13.8%)	27	11/158 (7%)	13
Abdominal Pain	11/152 (7.2%)	15	12/158 (7.6%)	22
Abdominal pain upper	12/152 (7.9%)	14	5/158 (3.2%)	7
Toothache	7/152 (4.6%)	9	9/158 (5.7%)	12
Constipation	4/152 (2.6%)	4	11/158 (7%)	11
Infections and infestations
Nasopharyngitis	45/152 (29.6%)	82	47/158 (29.7%)	68
Urinary Tract Infection	17/152 (11.2%)	19	12/158 (7.6%)	14
Gastroenteritis	13/152 (8.6%)	13	9/158 (5.7%)	11
Upper respiratory tract infection	9/152 (5.9%)	10	13/158 (8.2%)	17
Influenza	9/152 (5.9%)	12	16/158 (10.1%)	16
Nervous system disorders
Headache	43/152 (28.3%)	109	35/158 (22.2%)	121
Pregnancy, puerperium and perinatal conditions
Pre-eclampsia	8/152 (5.3%)	8	10/158 (6.3%)	10
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	11/152 (7.2%)	13	13/158 (8.2%)	17
Vascular disorders
Hypertension	5/152 (3.3%)	5	8/158 (5.1%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.