4T: Comparison of Insulin Detemir, Insulin Aspart and Biphasic Insulin Aspart 30 With OAD Treatment in Type 2 Diabetes

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT00184600

Collaborator

(none)

708

Enrollment

Locations

Arms

Duration (Months)

11.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is conducted in Europe.

The aim of this research study is to compare the efficacy (reduction in HbA1c and in blood glucose levels) of insulin detemir, insulin aspart and biphasic insulin aspart 30, when added to current OAD (oral anti-diabetic drug) treatment in subjects with type 2 diabetes and to verify the safety of use (number and severity of episodes of hypoglycaemia, body weight and side effects).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Diabetes Mellitus, Type 2	Drug: biphasic insulin aspart Drug: insulin detemir Drug: insulin aspart	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

708 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 36-month, Multi-centre, Open-label, Randomised, Parallel-group Trial Comparing the Safety, Efficacy and Durability of Adding a Basal Insulin Versus a Twice Daily Insulin Mixture Versus a Meal-time Rapid-Acting Insulin in Subjects With Type 2 Diabetes Inadequately Controlled on Therapy With Oral Agents, and Assessing the Requirement for More Complex Insulin Regimens to Achieve and Maintain Glycaemic Control, Their Efficacy and Durability

Study Start Date :

Nov 1, 2004

Actual Primary Completion Date :

Aug 1, 2009

Actual Study Completion Date :

Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin detemir (basal insulin) Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen.	Drug: insulin detemir Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart
Active Comparator: Insulin aspart (prandial insulin) Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen.	Drug: biphasic insulin aspart Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart
Active Comparator: Biphasic insulin aspart 30 (biphasic insulin) Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen.	Drug: insulin aspart Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, twice daily plus option for insulin detemir

Arm

Intervention/Treatment

Experimental: Insulin detemir (basal insulin)

Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen.

Drug: insulin detemir

Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart

Active Comparator: Insulin aspart (prandial insulin)

Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen.

Drug: biphasic insulin aspart

Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, once or twice daily plus option for insulin aspart

Active Comparator: Biphasic insulin aspart 30 (biphasic insulin)

Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. In the second and third years, a second insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen.

Drug: insulin aspart

Treat-to-target (individually adjusted dose), subcutaneously (under the skin) injection, twice daily plus option for insulin detemir

Outcome Measures

Primary Outcome Measures

HbA1c (Glycosylated Haemoglobin) at Month 12 [Baseline, Month 12]
HbA1c values offer evidence of the efficacy and durability of the insulin regimens.
HbA1c (Glycosylated Haemoglobin) at Month 36 [Baseline, Month 36]
HbA1c values offer evidence of the efficacy and durability of the insulin regimens.

Secondary Outcome Measures

Percentage of Participants (Total Participants and the Subset of Participants Who Did Not Have an Hypoglycaemic Episode) Achieving a Month 12 Value in HbA1c Below or Equal to 6.5% [Month 12]
Two participant counts are listed. The first is the percentage of total participants who achieved the target (HbA1c below or equal to 6.5%) at Month 12. The second is the percentage of subset of participants who achieved the target and did not have either minor or major hypoglycaemic episode within the four weeks prior to the month 12 exam. Minor hypoglycaemic episode is an episode in which the participant was able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major hypoglycaemic episode is an episode in which the participant was unable to treat her/himself.
Percentage of Participants Achieving a Month 36 Value in HbA1c Below or Equal to 6.5% [Month 36]
Percentage of participants who achieved the target (HbA1c below or equal to 6.5%) at Month 36
Number of Hypoglycaemic Events Per Participant Per Year at Month 12 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5% [Month 12]
Rate of hypoglycaemic events was calculated as the median number of events per participant per year, defined as grade 1 (symptoms only), 2 (minor) and 3 (major). Symptoms only if self-measured plasma glucose level of 3.1 mmol/L (56 mg/dL) or more. Minor (grade 2) if able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major (grade 3) if unable to treat her/himself. Rates are reported for all participants and for the subset of participants who achieved target HbA1c below or equal to 6.5%.
Number of Hypoglycaemic Events Per Participant Per Year at Month 36 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5% [Month 36]
Rate of hypoglycaemic events was calculated as the median number of events per participant per year, defined as grade 1 (symptoms only), 2 (minor) and 3 (major). Symptoms only if self-measured plasma glucose level of 3.1 mmol/L (56 mg/dL) or more. Minor (grade 2) if able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major (grade 3) if unable to treat her/himself. Rates are reported for all participants and for the subset of participants who achieved target HbA1c below or equal to 6.5%.
Percentage of Participants Who Required A Second Insulin Therapy by Month 12 [Month 12]
Percentage of participants who required a second insulin formulation to be added to their treatment. This outcome offers evidence to the efficacy and durability of the insulin regimens.
Percentage of Participants Who Required A Second Insulin Therapy by Month 36 [Month 36]
Percentage of participants who required a second insulin formulation to be added to their treatment. This outcome offers evidence to the efficacy and durability of the insulin regimens.
Change From Baseline in Body Weight at Month 12 [Week 0 (baseline), month 12]
Change From Baseline in Body Weight at Month 36 [Week 0 (baseline), month 36]
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months [Baseline, month 12]
For each visit and telephone contact, participants were asked to perform in advance three capillary glucose profiles (using blood glucose metre provided for the trial) obtained before breakfast and before the evening meal for participants in the biphasic and basal groups and before meals and two hours after meals and at bedtime in the prandial group.
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months [Baseline, month 36]
For each visit and telephone contact, participants were asked to perform in advance three capillary glucose profiles (using blood glucose metre provided for the trial) obtained before breakfast and before the evening meal for participants in the biphasic and basal groups and before meals and two hours after meals and at bedtime in the prandial group.
Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 12 Months [Month 12]
The EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) is a standardised instrument for use as a measure of health outcome in medical research. Responses can be used to generate a single numerical value associated with a given health state. The scale of values is graded from -0.59 to 1.00, with lower scores indicating a poorer health status. A score of 0 represents no quality of life and scores less than 0 represent states perceived by the respondent to be worse than death.
Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 36 Months [Month 36]
The EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) is a standardised instrument for use as a measure of health outcome in medical research. Responses can be used to generate a single numerical value associated with a given health state. The scale of values is graded from -0.59 to 1.00, with lower scores indicating a poorer health status. A score of 0 represents no quality of life and scores less than 0 represent states perceived by the respondent to be worse than death.
Number of Participants Having an 'Other' Adverse Event [Up to month 37 (36 months of treatment plus 1 month follow-up)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Type 2 diabetes
Insulin naive
On OAD treatment for at least 4 months with metformin, a sulphonylurea or a combination
Body Mass Index (BMI) below or equal to 40.0 kg/m2
HbA1c (glycosylated haemoglobin): 7.0%-10% (both inclusive)

Exclusion Criteria:

Proliferative retinopathy
Recurrent major hypoglycaemia
Cardial problems
Uncontrolled hypertension
Impaired hepatic or renal function

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Novo Nordisk Investigational Site	Dublin	Ireland	DUBLIN 15
2	Novo Nordisk Investigational Site	Dublin	Ireland	DUBLIN 7
3	Novo Nordisk Investigational Site	Dublin	Ireland	DUBLIN 8
4	Novo Nordisk Investigational Site	Galway	Ireland
5	Novo Nordisk Investigational Site	Aberdeen	United Kingdom	AB25 1LD
6	Novo Nordisk Investigational Site	Addlestone	United Kingdom	KT15 2BH
7	Novo Nordisk Investigational Site	Airdrie	United Kingdom	ML6 0JS
8	Novo Nordisk Investigational Site	Ashton-Under-Lyne	United Kingdom	OL6 9RW
9	Novo Nordisk Investigational Site	Ayr	United Kingdom	KA6 6DX
10	Novo Nordisk Investigational Site	Belfast	United Kingdom	BT12 6BA
11	Novo Nordisk Investigational Site	Belfast	United Kingdom	BT37 9RH
12	Novo Nordisk Investigational Site	Belfast	United Kingdom	BT9 78B
13	Novo Nordisk Investigational Site	Berkshire	United Kingdom	RG7 3SQ
14	Novo Nordisk Investigational Site	Birmingham	United Kingdom	B71 4HJ
15	Novo Nordisk Investigational Site	Birmingham	United Kingdom	B9 5SS
16	Novo Nordisk Investigational Site	Bournemouth	United Kingdom	BH7 7DW
17	Novo Nordisk Investigational Site	Bradford	United Kingdom	BD9 6RJ
18	Novo Nordisk Investigational Site	Bristol	United Kingdom	BS10 5NB
19	Novo Nordisk Investigational Site	Bury St Edmunds	United Kingdom	IP30 9QU
20	Novo Nordisk Investigational Site	Cambridge	United Kingdom	CB2 2QQ
21	Novo Nordisk Investigational Site	Colchester	United Kingdom	CO4 5JL
22	Novo Nordisk Investigational Site	Coventry	United Kingdom	CV1 4FH
23	Novo Nordisk Investigational Site	Crawley	United Kingdom	RH10 7DH
24	Novo Nordisk Investigational Site	Derby	United Kingdom	DE22 3DT
25	Novo Nordisk Investigational Site	Dundee	United Kingdom	DD1 9SY
26	Novo Nordisk Investigational Site	Edinburgh	United Kingdom	EH16 4SA
27	Novo Nordisk Investigational Site	Exeter	United Kingdom	EX2 5AX
28	Novo Nordisk Investigational Site	Gillingham	United Kingdom	ME7 5NY
29	Novo Nordisk Investigational Site	Glasgow	United Kingdom	G4 0SF
30	Novo Nordisk Investigational Site	Guildford	United Kingdom	GU2 7XX
31	Novo Nordisk Investigational Site	Haywards Heath	United Kingdom	RH16 4EX
32	Novo Nordisk Investigational Site	Headington	United Kingdom	OX3 7LE
33	Novo Nordisk Investigational Site	High Wycombe	United Kingdom	HP11 2TZ
34	Novo Nordisk Investigational Site	Hull	United Kingdom	HU3 2JZ
35	Novo Nordisk Investigational Site	Kettering	United Kingdom	NN16 8UZ
36	Novo Nordisk Investigational Site	Leeds	United Kingdom	LS9 7TF
37	Novo Nordisk Investigational Site	Leicester	United Kingdom	LE1 5WW
38	Novo Nordisk Investigational Site	Leicester	United Kingdom	LE5 4PW
39	Novo Nordisk Investigational Site	Liverpool	United Kingdom	L7 8XP
40	Novo Nordisk Investigational Site	Liverpool	United Kingdom	L9 7AL
41	Novo Nordisk Investigational Site	Livingstone	United Kingdom	EH54 6PP
42	Novo Nordisk Investigational Site	London	United Kingdom	N19 3UA
43	Novo Nordisk Investigational Site	London	United Kingdom	SE5 9RS
44	Novo Nordisk Investigational Site	London	United Kingdom
45	Novo Nordisk Investigational Site	Manchester	United Kingdom	M13 0JE
46	Novo Nordisk Investigational Site	Manchester	United Kingdom	M23 9LT
47	Novo Nordisk Investigational Site	Manchester	United Kingdom	M41 5SL
48	Novo Nordisk Investigational Site	Manchester	United Kingdom	M8 5RB
49	Novo Nordisk Investigational Site	Middlesborough	United Kingdom	TS3 4BW
50	Novo Nordisk Investigational Site	Newcastle	United Kingdom	NE29 0LR
51	Novo Nordisk Investigational Site	Newcastle	United Kingdom	NE4 6BE
52	Novo Nordisk Investigational Site	Norfolk	United Kingdom	NR4 7UZ
53	Novo Nordisk Investigational Site	Northampton	United Kingdom	NN1 5BD
54	Novo Nordisk Investigational Site	Nottingham	United Kingdom	NG7 2UH
55	Novo Nordisk Investigational Site	Plymouth	United Kingdom	PL8 8DQ
56	Novo Nordisk Investigational Site	Rugby	United Kingdom	CV22 5PX
57	Novo Nordisk Investigational Site	Sheffield	United Kingdom	S5 7AU
58	Novo Nordisk Investigational Site	Skipton	United Kingdom	BD23 1EU
59	Novo Nordisk Investigational Site	Stevenage	United Kingdom	SG1 4AB
60	Novo Nordisk Investigational Site	Torquay	United Kingdom	TQ2 7AA
61	Novo Nordisk Investigational Site	Welwyn Garden City	United Kingdom	AL7 4HQ
62	Novo Nordisk Investigational Site	Whiston	United Kingdom	L35 5DR
63	Novo Nordisk Investigational Site	Wirral, Merseyside	United Kingdom	CH63 4JY

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:

NCT00184600

Other Study ID Numbers:

NN304-1613
2004-000514-38

First Posted:

Sep 16, 2005

Last Update Posted:

Mar 9, 2017

Last Verified:

Jan 1, 2017

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Insulin degludec, insulin aspart drug combination

Insulin Detemir

Biphasic Insulins

Study Results

Participant Flow

Recruitment Details	58 sites across the United Kingdom and Ireland. Recruitment period: November 2004-August 2006
Pre-assignment Detail	Eligible subjects continued their current oral anti-diabetic drug (OAD) treatment (metformin and/or sulphonylurea) without changing the dose throughout the trial. Subjects were asked not to alter their current diet and activities throughout the trial unless clinically necessary. Subjects fasted from 22:00 the evening prior to randomisation.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Period Title: Overall Study
STARTED	234	239	235
COMPLETED	189	188	201
NOT COMPLETED	45	51	34

Baseline Characteristics

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)	Total
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen	Total of all reporting groups
Overall Participants	234	239	235	708
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.87 (9.97)	61.60 (10.54)	61.67 (8.93)	61.7 (9.8)
Sex: Female, Male (Count of Participants)
Female	91 38.9%	87 36.4%	76 32.3%	254 35.9%
Male	143 61.1%	152 63.6%	159 67.7%	454 64.1%
Race/Ethnicity, Customized (participants) [Number]
White	218 93.2%	214 89.5%	221 94%	653 92.2%
Mixed	2 0.9%	4 1.7%	1 0.4%	7 1%
Asian / Asian British	9 3.8%	15 6.3%	11 4.7%	35 4.9%
Black / Black British	2 0.9%	5 2.1%	2 0.9%	9 1.3%
Other	3 1.3%	1 0.4%	0 0%	4 0.6%
Smoking (participants) [Number]
Non Smoker, Never Smoked	106 45.3%	88 36.8%	82 34.9%	276 39%
Ex Smoker	95 40.6%	108 45.2%	120 51.1%	323 45.6%
Current Smoker	33 14.1%	43 18%	33 14%	109 15.4%
Oral Anti-Diabetic Drugs (OADs) (participants) [Number]
Metformin	2 0.9%	0 0%	4 1.7%	6 0.8%
Sulphonylurea	8 3.4%	12 5%	10 4.3%	30 4.2%
Metformin + Sulphonylurea	224 95.7%	227 95%	221 94%	672 94.9%
Diabetic complication, Retinopathy (participants) [Number]
Yes	43 18.4%	45 18.8%	34 14.5%	122 17.2%
No	191 81.6%	194 81.2%	201 85.5%	586 82.8%
Diabetic complication, Neuropathy (participants) [Number]
Yes	39 16.7%	55 23%	41 17.4%	135 19.1%
No	195 83.3%	184 77%	194 82.6%	573 80.9%
Diabetic complication, Nephropathy (participants) [Number]
Yes	23 9.8%	24 10%	21 8.9%	68 9.6%
No	211 90.2%	215 90%	214 91.1%	640 90.4%
Diabetic complication, Macroaniopathy (participants) [Number]
Yes	44 18.8%	42 17.6%	52 22.1%	138 19.5%
No	190 81.2%	197 82.4%	183 77.9%	570 80.5%
Duration of diabetes (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	9 (5.13)	9 (5.54)	9 (5.23)	9
Alcohol (units) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units]	4 (9.16)	5 (7.88)	6 (9.61)	5
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	85.52 (16.25)	84.92 (14.43)	86.91 (16.82)	85.8 (15.9)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.82 (4.59)	29.74 (4.51)	30.34 (4.73)	29.8 (4.6)
Waist (cm) [Mean (Standard Deviation) ]
Men	104 (12)	102 (11)	104 (12)	103 (12)
Women	97 (12)	100 (11)	98 (13)	98 (12)
Eight-point Capillary Plasma Glucose Profiles (mg/dL) [Mean (Standard Deviation) ]
All time pointsexcluding 3 am	196 (43)	200 (49)	202 (47)	200 (47)
Fasting plasma	171 (47)	173 (49)	175 (50)	173 (49)
Postprandial	223 (50)	227 (56)	229 (54)	227 (54)
At 3 am	164 (56)	164 (59)	171 (58)	166 (58)

Outcome Measures

1. Primary Outcome

Title	HbA1c (Glycosylated Haemoglobin) at Month 12
Description	HbA1c values offer evidence of the efficacy and durability of the insulin regimens.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Baseline	8.45 (0.80)	8.55 (0.78)	8.63 (0.81)
Month 12	7.64 (0.96)	7.20 (1.06)	7.33 (0.95)

2. Primary Outcome

Title	HbA1c (Glycosylated Haemoglobin) at Month 36
Description	HbA1c values offer evidence of the efficacy and durability of the insulin regimens.
Time Frame	Baseline, Month 36

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Baseline	8.45 (0.80)	8.55 (0.78)	8.63 (0.81)
Month 36	7.11 (1.13)	7.04 (1.17)	7.22 (1.11)

3. Secondary Outcome

Title	Percentage of Participants (Total Participants and the Subset of Participants Who Did Not Have an Hypoglycaemic Episode) Achieving a Month 12 Value in HbA1c Below or Equal to 6.5%
Description	Two participant counts are listed. The first is the percentage of total participants who achieved the target (HbA1c below or equal to 6.5%) at Month 12. The second is the percentage of subset of participants who achieved the target and did not have either minor or major hypoglycaemic episode within the four weeks prior to the month 12 exam. Minor hypoglycaemic episode is an episode in which the participant was able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major hypoglycaemic episode is an episode in which the participant was unable to treat her/himself.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Total participants who achieved target	8.1 3.5%	23.9 10%	17.0 7.2%
Subset who achieved target, n=18, 50, 39	78.9 33.7%	43.9 18.4%	52.5 22.3%

4. Secondary Outcome

Title	Percentage of Participants Achieving a Month 36 Value in HbA1c Below or Equal to 6.5%
Description	Percentage of participants who achieved the target (HbA1c below or equal to 6.5%) at Month 36
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Number [percentage of participants]	43.2 18.5%	44.8 18.7%	31.9 13.6%

5. Secondary Outcome

Title	Number of Hypoglycaemic Events Per Participant Per Year at Month 12 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5%
Description	Rate of hypoglycaemic events was calculated as the median number of events per participant per year, defined as grade 1 (symptoms only), 2 (minor) and 3 (major). Symptoms only if self-measured plasma glucose level of 3.1 mmol/L (56 mg/dL) or more. Minor (grade 2) if able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major (grade 3) if unable to treat her/himself. Rates are reported for all participants and for the subset of participants who achieved target HbA1c below or equal to 6.5%.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
All participants, Grade 1	2.0	8.0	5.0
All participants, Grade 2	0	8.0	3.9
All participants, Grade 3	0	0	0
All participants, Grade 2 or 3	0	8.0	3.9
Achieved HbA1c target, Grade 1, n=18, 50, 39	3.9	7.8	5.4
Achieved HbA1c target, Grade 2, n=18, 50, 39	3.0	8.0	4.0
Achieved HbA1c target, Grade 3, n=18, 50, 39	0	0	0
Achieved HbA1c target, Grade 2 or 3, n=18, 50, 39	3.0	8.7	4.0

6. Secondary Outcome

Title	Number of Hypoglycaemic Events Per Participant Per Year at Month 36 for All Participants and the Subset Who Achieved Target HbA1c Below or Equal to 6.5%
Description	Rate of hypoglycaemic events was calculated as the median number of events per participant per year, defined as grade 1 (symptoms only), 2 (minor) and 3 (major). Symptoms only if self-measured plasma glucose level of 3.1 mmol/L (56 mg/dL) or more. Minor (grade 2) if able to treat her/himself and plasma glucose was below 3.1 mmol/L (56 mg/dL). Major (grade 3) if unable to treat her/himself. Rates are reported for all participants and for the subset of participants who achieved target HbA1c below or equal to 6.5%.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
All participants, Grade 1	2.7	5.7	3.8
All participants, Grade 2	1.7	5.5	3.0
All participants, Grade 3	0	0	0
All participants, Grade 2 or 3	1.7	5.7	3.0
Achieved HbA1c target, Grade 1, n=73, 70, 55	3.0	5.7	3.0
Achieved HbA1c target, Grade 2, n=73, 70, 55	2.0	5.3	2.7
Achieved HbA1c target, Grade 3, n=73, 70, 55	0	0	0
Achieved HbA1c target, Grade 2 or 3, n=73, 70, 55	2.0	5.5	3.0

7. Secondary Outcome

Title	Percentage of Participants Who Required A Second Insulin Therapy by Month 12
Description	Percentage of participants who required a second insulin formulation to be added to their treatment. This outcome offers evidence to the efficacy and durability of the insulin regimens.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Number [percentage of participants]	17.9 7.6%	4.2 1.8%	8.9 3.8%

8. Secondary Outcome

Title	Percentage of Participants Who Required A Second Insulin Therapy by Month 36
Description	Percentage of participants who required a second insulin formulation to be added to their treatment. This outcome offers evidence to the efficacy and durability of the insulin regimens.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Number [percentage of participants]	89 38%	82 34.3%	88 37.4%

9. Secondary Outcome

Title	Change From Baseline in Body Weight at Month 12
Description
Time Frame	Week 0 (baseline), month 12

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Mean (Standard Deviation) [kilogram]	1.9 (4.2)	5.7 (4.6)	4.7 (4.0)

10. Secondary Outcome

Title	Change From Baseline in Body Weight at Month 36
Description
Time Frame	Week 0 (baseline), month 36

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Mean (Standard Deviation) [kilograms]	3.6 (0.5)	6.4 (0.5)	5.7 (0.5)

11. Secondary Outcome

Title	Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months
Description	For each visit and telephone contact, participants were asked to perform in advance three capillary glucose profiles (using blood glucose metre provided for the trial) obtained before breakfast and before the evening meal for participants in the biphasic and basal groups and before meals and two hours after meals and at bedtime in the prandial group.
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
All timepoints excluding 3am	-43 (43)	-65 (43)	-59 (54)
Fasting	-59 (52)	-23 (49)	-45 (56)
Postprandial	-47 (54)	-83 (54)	-68 (63)
3am	-40 (70)	-34 (59)	-52 (70)

12. Secondary Outcome

Title	Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months
Description	For each visit and telephone contact, participants were asked to perform in advance three capillary glucose profiles (using blood glucose metre provided for the trial) obtained before breakfast and before the evening meal for participants in the biphasic and basal groups and before meals and two hours after meals and at bedtime in the prandial group.
Time Frame	Baseline, month 36

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
All timepoints excluding 3am	-58 (43)	-67 (47)	-56 (47)
Fasting	-47 (49)	-49 (45)	-50 (47)
Postprandial	-67 (50)	-85 (59)	-61 (58)
3am	-45 (77)	-27 (70)	-38 (77)

13. Secondary Outcome

Title	Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 12 Months
Description	The EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) is a standardised instrument for use as a measure of health outcome in medical research. Responses can be used to generate a single numerical value associated with a given health state. The scale of values is graded from -0.59 to 1.00, with lower scores indicating a poorer health status. A score of 0 represents no quality of life and scores less than 0 represent states perceived by the respondent to be worse than death.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Mean (95% Confidence Interval) [units on a scale]	0.78	0.76	0.76

14. Secondary Outcome

Title	Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 36 Months
Description	The EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) is a standardised instrument for use as a measure of health outcome in medical research. Responses can be used to generate a single numerical value associated with a given health state. The scale of values is graded from -0.59 to 1.00, with lower scores indicating a poorer health status. A score of 0 represents no quality of life and scores less than 0 represent states perceived by the respondent to be worse than death.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description
Intention to treat analyses (ITT) included all those randomised. Missing data was imputed by SAS Proc MI (Multiple Imputation), using the non-parametric Propensity Score method for data with monotone missing pattern under the assumption of non-normality and the Bayesian Monte Carlo Markov Chain approach for data with values missing intermittently.

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Mean (95% Confidence Interval) [units on a scale]	0.80	0.77	0.76

15. Secondary Outcome

Title	Number of Participants Having an 'Other' Adverse Event
Description
Time Frame	Up to month 37 (36 months of treatment plus 1 month follow-up)

Outcome Measure Data

Analysis Population Description
Safety population consisting of all randomised participants exposed to at least one dose of trial drug(s).

Arm/Group Title	Insulin Detemir (Basal Insulin)	Insulin Aspart (Prandial Insulin)	Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen	Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen	Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
Measure Participants	234	239	235
Number [participants]	227 97%	235 98.3%	228 97%

Adverse Events

	Insulin Detemir (Basal Insulin)		Insulin Aspart (Prandial Insulin)		Biphasic Insulin Aspart 30 (Biphasic Insulin)
Time Frame	The adverse events were collected from the first trial-related activity once the subject had signed the informed consent, up until 28 days after the last clinic visit. Total reporting period for adverse events was 162 weeks.
Adverse Event Reporting Description	The safety analysis set contains all randomised subjects exposed to at least one dose of trial drug(s).

Arm/Group Title	Insulin Detemir (Basal Insulin)		Insulin Aspart (Prandial Insulin)		Biphasic Insulin Aspart 30 (Biphasic Insulin)
Arm/Group Description	Individually adjusted insulin detemir injected subcutaneously once daily before bed and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. Subjects had the option to add a second pre-breakfast basal insulin analogue injection if pre-breakfast but not pre-dinner meal plasma glucose targets were met. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin detemir once (or twice) daily were asked to add insulin aspart three times daily with meals i.e. a basal-bolus insulin analogue regimen		Individually adjusted insulin aspart injected subcutaneously at meal-times (breakfast, lunch and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to insulin aspart three times a day with meals were asked to add insulin detemir once or twice daily i.e. a basal-bolus insulin analogue regimen		Individually adjusted biphasic insulin aspart 30 injected subcutaneously twice daily with meals (breakfast and dinner) and administered in combination with current OAD treatment. At week 24 and thereafter, if two consecutive measurements of HbA1c were at least 8%, or one measurement of HbA1c was at least 10% the subject was deemed to have unacceptable hyperglycaemia and a second insulin formulation was added. In the second and third years, a third insulin formulation was added if subjects failed to achieve or to maintain good glycaemic control, defined as two consecutive HbA1c measurements exceeding 6.5% or a single measurement exceeding 7.5%. Subjects randomised to biphasic insulin aspart twice daily were asked to add insulin aspart at lunchtime (midday) i.e. an augmented pre-mixed insulin analogue regimen
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Detemir (Basal Insulin)		Insulin Aspart (Prandial Insulin)		Biphasic Insulin Aspart 30 (Biphasic Insulin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/234 (33.3%)		79/239 (33.1%)		105/235 (44.7%)
Blood and lymphatic system disorders
Anaemia	1/234 (0.4%)	1	1/239 (0.4%)	1	1/235 (0.4%)	1
Iron deficiency anaemia	0/234 (0%)	0	1/239 (0.4%)	1	4/235 (1.7%)	4
Pernicious anaemia	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Cardiac disorders
Acute coronary syndrome	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Acute left ventricular failure	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Acute myocardial infarction	2/234 (0.9%)	2	1/239 (0.4%)	1	2/235 (0.9%)	2
Angina pectoris	4/234 (1.7%)	5	2/239 (0.8%)	4	8/235 (3.4%)	11
Angina unstable	3/234 (1.3%)	3	1/239 (0.4%)	1	0/235 (0%)	0
Aortic valve incompetence	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Aortic valve stenosis	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Arteriosclerosis coronary artery	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Atrial fibrillation	1/234 (0.4%)	2	1/239 (0.4%)	1	1/235 (0.4%)	2
Atrial flutter	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	2
Atrioventricular block	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Atrioventricular block complete	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Atrioventricular block second degree	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Bradycardia	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Cardiac arrest	1/234 (0.4%)	1	1/239 (0.4%)	1	0/235 (0%)	0
Cardiac failure	1/234 (0.4%)	1	3/239 (1.3%)	5	2/235 (0.9%)	2
Cardiac failure acute	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Cardiac failure congestive	3/234 (1.3%)	3	1/239 (0.4%)	1	4/235 (1.7%)	5
Coronary artery disease	0/234 (0%)	0	2/239 (0.8%)	2	2/235 (0.9%)	2
Coronary artery occlusion	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Coronary artery stenosis	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Left ventribular dysfunction	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Left ventricular failure	2/234 (0.9%)	2	1/239 (0.4%)	1	2/235 (0.9%)	2
Myocardial infarction	6/234 (2.6%)	6	4/239 (1.7%)	4	2/235 (0.9%)	2
Myocardial ischaemia	1/234 (0.4%)	1	4/239 (1.7%)	4	2/235 (0.9%)	2
Palpitations	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Right ventricular failure	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Sinus bradycardia	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Tricuspid valve incompetence	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Endocrine disorders
Goitre	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Eye disorders
Cataract	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Diabetic retinopathy	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Eyelid ptosis	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Optic ischaemic neuropathy	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Retinal detachment	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Vision blurred	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Gastrointestinal disorders
Abdominal distension	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Abdominal pain	1/234 (0.4%)	2	1/239 (0.4%)	1	5/235 (2.1%)	5
Anal fissure	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Ascites	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Change of bowel habit	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Coeliac disease	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Colitis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Colitis ulcerative	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Constipation	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Crohn's disease	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Diarrhoea	1/234 (0.4%)	1	2/239 (0.8%)	2	2/235 (0.9%)	2
Diverticulum	0/234 (0%)	0	2/239 (0.8%)	3	1/235 (0.4%)	1
Duodenal ulcer	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Dyspepsia	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Epigastric discomfort	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Faeces discoloured	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Food poisoning	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Gastric ulcer	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Gastritis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Gastritis haemorrhagic	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Gastrointestinal haemorrhage	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Gastrooesophageal reflux disease	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Haematemesis	1/234 (0.4%)	1	0/239 (0%)	0	2/235 (0.9%)	2
Haematochezia	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Inguinal hernia	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Intestinal ischaemia	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Intestinal obstruction	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Melaena	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Nausea	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Oesophageal food impaction	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	2
Oesophageal rupture	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Oesophageal spasm	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Oesophageal ulcer	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Oesophagitis	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Pancreatic pseudocyst	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Pancreatitis	1/234 (0.4%)	1	1/239 (0.4%)	1	2/235 (0.9%)	2
Pancreatitis chronic	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Pancreatolithiasis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Peptic ulcer	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Rectal haemorrhage	2/234 (0.9%)	2	0/239 (0%)	0	1/235 (0.4%)	1
Small intestinal haemorrhage	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Umbilical hernia	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Vomiting	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
General disorders
Adverse drug reaction	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Asthenia	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Chest discomfort	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Chest pain	5/234 (2.1%)	5	1/239 (0.4%)	6	3/235 (1.3%)	3
Dislocation of joint prosthesis	1/234 (0.4%)	2	0/239 (0%)	0	0/235 (0%)	0
Gait disturbance	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Multi-organ failure	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Non-cardiac chest pain	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Oedema peripheral	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Pyrexia	1/234 (0.4%)	1	1/239 (0.4%)	1	0/235 (0%)	0
Hepatobiliary disorders
Alcoholic liver disease	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	2
Cholecystitis	1/234 (0.4%)	1	1/239 (0.4%)	1	0/235 (0%)	0
Cholelithiasis	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Infections and infestations
Abdominal abscess	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Abscess limb	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Anal abscess	2/234 (0.9%)	2	0/239 (0%)	0	0/235 (0%)	0
Biliary sepsis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Bronchiectasis	0/234 (0%)	0	1/239 (0.4%)	1	2/235 (0.9%)	2
Bronchitis	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Bronchpulmonary aspergillosis allergic	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Campylobacter gastroenteritis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Cellulitis	0/234 (0%)	0	1/239 (0.4%)	1	6/235 (2.6%)	6
Cellulitis orbital	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Clostridial infection	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Clostridium difficile colitis	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Diverticulitis	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Gangrene	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Gastroenteritis	2/234 (0.9%)	2	0/239 (0%)	0	4/235 (1.7%)	4
Graft infection	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Infected skin ulcer	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Infective exacerbation of chronic obstructive airways	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Labyrinthitis	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Lobar pneumonia	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Localised infection	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Lower respiratory tract infection	0/234 (0%)	0	2/239 (0.8%)	2	3/235 (1.3%)	3
Nail infection	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Perineal abscess	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Pilonidal cyst	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Pneumonia	1/234 (0.4%)	1	1/239 (0.4%)	1	2/235 (0.9%)	2
Postoperative wound infection	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Pyelonephritis	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Respiratory tract infection	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Scrotal abscess	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Sepsis	2/234 (0.9%)	2	0/239 (0%)	0	2/235 (0.9%)	2
Staphylococcal osteomyelitis	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Stent related infection	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	2
Upper respiratory tract infection	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Urinary tract infection	1/234 (0.4%)	1	1/239 (0.4%)	1	3/235 (1.3%)	3
Wound infection	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	3/234 (1.3%)	3	0/239 (0%)	0	0/235 (0%)	0
Ankle fracture	1/234 (0.4%)	1	1/239 (0.4%)	1	0/235 (0%)	0
Back injury	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Brain contusion	1/234 (0.4%)	2	0/239 (0%)	0	0/235 (0%)	0
Chest injury	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Drug dispensing error	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Fall	0/234 (0%)	0	2/239 (0.8%)	2	2/235 (0.9%)	2
Femoral neck fracture	1/234 (0.4%)	1	1/239 (0.4%)	1	3/235 (1.3%)	3
Head injury	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Hip fracture	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Incisional hernia	1/234 (0.4%)	1	1/239 (0.4%)	1	0/235 (0%)	0
Intentional overdose	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Joint injury	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Joint sprain	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Ligament rupture	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Medication error	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Meniscus lesion	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Post procedural complication	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Radius fracture	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Skull fracture base	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Subdural haemorrhage	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Tibia fracture	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Wrist fracture	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Wrong drug administered	2/234 (0.9%)	2	1/239 (0.4%)	1	0/235 (0%)	0
Investigations
Biopsy liver	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Catheterisation cardiac	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
International normalised ratio increased	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Pulse absent	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Smear cervix abnormal	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/234 (0.4%)	1	1/239 (0.4%)	1	0/235 (0%)	0
Diabetes mellitus inadequate control	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Fluid retention	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Hypoglycaemia	5/234 (2.1%)	7	13/239 (5.4%)	13	12/235 (5.1%)	14
Hypoglycaemic unconsciousness	3/234 (1.3%)	3	0/239 (0%)	0	1/235 (0.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Arthritis	1/234 (0.4%)	1	1/239 (0.4%)	1	0/235 (0%)	0
Back pain	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Dupuytren's contracture operation	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Foot deformity	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Groin pain	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Haemarthrosis	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Intervertebral disc compression	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Intervertebral disc protrusion	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Lower extremity mass	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Muscle haemorrhage	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Muscular weakness	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Musculoskeletal chest pain	1/234 (0.4%)	1	2/239 (0.8%)	2	0/235 (0%)	0
Musculoskeletal pain	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Neuropathic arthropathy	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Osteoarthritis	4/234 (1.7%)	4	1/239 (0.4%)	1	6/235 (2.6%)	7
Osteoporosis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Pain in extremity	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Periarthritis	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Polymyalgia rheumatica	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Rheumatoid arthritis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Synovitis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Basal cell carcinoma	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Basosquamous carcinoma	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Benign breast neoplasm	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Bladder papilloma	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Bladder transitional cell carcinoma	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Borderline ovarian tumour	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Colon cancer	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Colon cancer stage I	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Endometrial cancer	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Endometrial cancer stage III	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Galbladder cancer	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Hepatic neoplasm malignant recurrent	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Laryngeal cancer	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Leiomyosarcoma metastatic	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Lung neoplasm malignant	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Metastases to liver	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Metastases to lung	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Metastatic neoplasm	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Non-small cell lung cancer metastatic	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Non-small cell lung cancer stage IIIB	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Pancreatic carcinoma	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Prostate cancer	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Rectal cancer metastatic	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Rectal cancer stage III	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Transitional cell carcinoma	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Nervous system disorders
Carotid artery occlusion	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Carotid artery stenosis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Carpal tunnel syndrome	0/234 (0%)	0	1/239 (0.4%)	1	3/235 (1.3%)	3
Cerebral haemorrhage	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Cerebral infarction	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Cerebrovascular accident	2/234 (0.9%)	2	0/239 (0%)	0	3/235 (1.3%)	3
Cognitive disorder	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Dizziness	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Hypoglycaemic coma	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Lacunar infarction	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Loss of consciousness	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Neuropathy peripheral	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Paraesthesia	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Pneumocephalus	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Presyncope	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Radiculitis brachial	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Sensory loss	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Spinal cord compression	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Subarachnoid haemorrhage	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Transient ischaemic attack	0/234 (0%)	0	1/239 (0.4%)	1	2/235 (0.9%)	2
Psychiatric disorders
Anxiety	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Anxiety disorder	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Confusional state	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Depression	1/234 (0.4%)	1	0/239 (0%)	0	1/235 (0.4%)	1
Panic attack	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Renal and urinary disorders
Calculus ureteric	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Dysuria	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Haematuria	0/234 (0%)	0	2/239 (0.8%)	2	1/235 (0.4%)	1
Nephrolithiasis	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Renal colic	0/234 (0%)	0	1/239 (0.4%)	1	2/235 (0.9%)	2
Renal failure	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Renal failure acute	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Renal failure chronic	0/234 (0%)	0	1/239 (0.4%)	2	0/235 (0%)	0
Renal impairment	1/234 (0.4%)	1	1/239 (0.4%)	1	2/235 (0.9%)	2
Urethral meatus stenosis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Urethral stenosis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Urinary retention	1/234 (0.4%)	1	1/239 (0.4%)	1	2/235 (0.9%)	2
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Haematospermia	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Ovarian cyst	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Prostatomegaly	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Vaginal haemorrhage	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Asthma	2/234 (0.9%)	3	1/239 (0.4%)	1	0/235 (0%)	0
Chronic obstructive pulmonary disease	1/234 (0.4%)	1	2/239 (0.8%)	2	1/235 (0.4%)	1
Dysphonia	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Dyspnoea	3/234 (1.3%)	3	3/239 (1.3%)	3	3/235 (1.3%)	3
Epistaxis	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Pleural effusion	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Pulmonary embolism	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Pulmonary oedema	3/234 (1.3%)	3	2/239 (0.8%)	2	0/235 (0%)	0
Respiratory failure	0/234 (0%)	0	0/239 (0%)	0	2/235 (0.9%)	2
Sleep apnoea syndrome	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Wegener's granulomatosis	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Ingrowing nail	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Lichen sclerosus	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	4
Pruritis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Skin ulcer	2/234 (0.9%)	2	0/239 (0%)	0	0/235 (0%)	0
Surgical and medical procedures
Knee arthroplasty	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Penile prosthesis insertion	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Umbilical hernia repair	0/234 (0%)	0	1/239 (0.4%)	1	0/235 (0%)	0
Vascular disorders
Arterial stenosis limb	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Circulatory collapse	0/234 (0%)	0	4/239 (1.7%)	4	0/235 (0%)	0
Deep vein thrombosis	0/234 (0%)	0	1/239 (0.4%)	1	1/235 (0.4%)	1
Femoral arterial stenosis	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Femoral artery occlusion	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Haematoma	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Hypotension	0/234 (0%)	0	2/239 (0.8%)	2	0/235 (0%)	0
Intermittent claudication	2/234 (0.9%)	2	2/239 (0.8%)	2	0/235 (0%)	0
Ischaemia	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Peripheral vascular disorder	1/234 (0.4%)	1	1/239 (0.4%)	3	0/235 (0%)	0
Varicose vein	1/234 (0.4%)	1	0/239 (0%)	0	0/235 (0%)	0
Vasculitis	0/234 (0%)	0	0/239 (0%)	0	1/235 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Insulin Detemir (Basal Insulin)		Insulin Aspart (Prandial Insulin)		Biphasic Insulin Aspart 30 (Biphasic Insulin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	227/234 (97%)		235/239 (98.3%)		228/235 (97%)
Blood and lymphatic system disorders
Anaemia	19/234 (8.1%)	19	13/239 (5.4%)	14	14/235 (6%)	16
Eye disorders
Diabetic retinopathy	19/234 (8.1%)	20	10/239 (4.2%)	10	4/235 (1.7%)	4
Gastrointestinal disorders
Abdominal discomfort	14/234 (6%)	33	16/239 (6.7%)	24	27/235 (11.5%)	40
Abdominal pain	9/234 (3.8%)	12	7/239 (2.9%)	7	14/235 (6%)	20
Diarrhoea	60/234 (25.6%)	115	53/239 (22.2%)	75	45/235 (19.1%)	63
Dyspepsia	21/234 (9%)	38	14/239 (5.9%)	15	13/235 (5.5%)	19
Vomiting	45/234 (19.2%)	80	44/239 (18.4%)	68	43/235 (18.3%)	71
General disorders
Fatigue	12/234 (5.1%)	15	10/239 (4.2%)	12	4/235 (1.7%)	7
Injection site haematoma	39/234 (16.7%)	49	34/239 (14.2%)	50	34/235 (14.5%)	46
Injection site mass	18/234 (7.7%)	23	7/239 (2.9%)	7	16/235 (6.8%)	21
Malaise	15/234 (6.4%)	38	18/239 (7.5%)	38	18/235 (7.7%)	27
Infections and infestations
Bronchitis	12/234 (5.1%)	17	10/239 (4.2%)	13	6/235 (2.6%)	17
Ear infection	6/234 (2.6%)	8	11/239 (4.6%)	15	17/235 (7.2%)	17
Gastroenteritis	10/234 (4.3%)	13	8/239 (3.3%)	12	14/235 (6%)	15
Infection	50/234 (21.4%)	84	55/239 (23%)	88	59/235 (25.1%)	89
Influenza	37/234 (15.8%)	55	29/239 (12.1%)	33	33/235 (14%)	43
Localised infection	9/234 (3.8%)	13	12/239 (5%)	14	16/235 (6.8%)	20
Nasopharyngitis	108/234 (46.2%)	251	97/239 (40.6%)	211	99/235 (42.1%)	208
Pharyngitis	13/234 (5.6%)	17	8/239 (3.3%)	8	7/235 (3%)	9
Upper respiratory tract infection	33/234 (14.1%)	51	28/239 (11.7%)	51	27/235 (11.5%)	35
Urinary tract infection	32/234 (13.7%)	67	24/239 (10%)	31	30/235 (12.8%)	60
Viral infection	12/234 (5.1%)	12	10/239 (4.2%)	13	13/235 (5.5%)	17
Injury, poisoning and procedural complications
Fall	20/234 (8.5%)	24	20/239 (8.4%)	23	16/235 (6.8%)	20
Musculoskeletal and connective tissue disorders
Arthralgia	15/234 (6.4%)	16	23/239 (9.6%)	32	25/235 (10.6%)	32
Back pain	31/234 (13.2%)	40	38/239 (15.9%)	42	28/235 (11.9%)	35
Joint swelling	14/234 (6%)	15	14/239 (5.9%)	14	8/235 (3.4%)	8
Muscle spasms	11/234 (4.7%)	14	13/239 (5.4%)	15	7/235 (3%)	11
Pain in extremity	30/234 (12.8%)	37	31/239 (13%)	35	36/235 (15.3%)	41
Nervous system disorders
Dizziness	20/234 (8.5%)	28	16/239 (6.7%)	23	15/235 (6.4%)	17
Paraesthesia	13/234 (5.6%)	13	11/239 (4.6%)	16	13/235 (5.5%)	18
Psychiatric disorders
Depression	8/234 (3.4%)	10	12/239 (5%)	12	16/235 (6.8%)	16
Respiratory, thoracic and mediastinal disorders
Cough	48/234 (20.5%)	66	51/239 (21.3%)	63	38/235 (16.2%)	46
Dyspnoea	13/234 (5.6%)	15	20/239 (8.4%)	24	13/235 (5.5%)	14
Oropharyngeal pain	35/234 (15%)	51	31/239 (13%)	55	27/235 (11.5%)	37
Skin and subcutaneous tissue disorders
Rash	11/234 (4.7%)	14	12/239 (5%)	12	14/235 (6%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Novo Nordisk reserves the right to not release data until specified milestones are reached. This includes the right to not release interim results of clinical trials, because that can invalidate results of the entire trial. At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.

Results Point of Contact

Name/Title	Public Access to Clinical Trials
Organization	Novo Nordisk A/S
Phone
Email	clinicaltrials@novonordisk.com

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT00184600

Other Study ID Numbers:

NN304-1613
2004-000514-38

First Posted:

Sep 16, 2005

Last Update Posted:

Mar 9, 2017

Last Verified:

Jan 1, 2017

4T: Comparison of Insulin Detemir, Insulin Aspart and Biphasic Insulin Aspart 30 With OAD Treatment in Type 2 Diabetes

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact