Trial Outcomes & Findings for Comparison of Insulin Detemir, Insulin Aspart and Biphasic Insulin Aspart 30 With OAD Treatment in Type 2 Diabetes (NCT NCT00184600)

NCT ID: NCT00184600

Last Updated: 2017-03-09

Results Overview

HbA1c values offer evidence of the efficacy and durability of the insulin regimens.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

708 participants

Primary outcome timeframe

Baseline, Month 12

Results posted on

2017-03-09

Participant Flow

58 sites across the United Kingdom and Ireland. Recruitment period: November 2004-August 2006

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.

Participant milestones

Participant milestones
Measure	Insulin Detemir (Basal Insulin) 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	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. 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	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. 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
Overall Study STARTED	234	239	235
Overall Study COMPLETED	189	188	201
Overall Study NOT COMPLETED	45	51	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Detemir (Basal Insulin) 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	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. 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	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. 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
Overall Study Adverse Event	9	0	5
Overall Study Death	3	9	7
Overall Study Lack of Efficacy	3	1	3
Overall Study Lost to Follow-up	4	6	1
Overall Study Protocol Violation	2	2	3
Overall Study Withdrawal by Subject	20	28	12
Overall Study Unclassified	4	5	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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 n=708 Participants Total of all reporting groups
Age, Continuous	61.87 years STANDARD_DEVIATION 9.97 • n=5 Participants	61.60 years STANDARD_DEVIATION 10.54 • n=7 Participants	61.67 years STANDARD_DEVIATION 8.93 • n=5 Participants	61.7 years STANDARD_DEVIATION 9.8 • n=4 Participants
Sex: Female, Male Female	91 Participants n=5 Participants	87 Participants n=7 Participants	76 Participants n=5 Participants	254 Participants n=4 Participants
Sex: Female, Male Male	143 Participants n=5 Participants	152 Participants n=7 Participants	159 Participants n=5 Participants	454 Participants n=4 Participants
Race/Ethnicity, Customized White	218 participants n=5 Participants	214 participants n=7 Participants	221 participants n=5 Participants	653 participants n=4 Participants
Race/Ethnicity, Customized Mixed	2 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants
Race/Ethnicity, Customized Asian / Asian British	9 participants n=5 Participants	15 participants n=7 Participants	11 participants n=5 Participants	35 participants n=4 Participants
Race/Ethnicity, Customized Black / Black British	2 participants n=5 Participants	5 participants n=7 Participants	2 participants n=5 Participants	9 participants n=4 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants
Smoking Non Smoker, Never Smoked	106 participants n=5 Participants	88 participants n=7 Participants	82 participants n=5 Participants	276 participants n=4 Participants
Smoking Ex Smoker	95 participants n=5 Participants	108 participants n=7 Participants	120 participants n=5 Participants	323 participants n=4 Participants
Smoking Current Smoker	33 participants n=5 Participants	43 participants n=7 Participants	33 participants n=5 Participants	109 participants n=4 Participants
Oral Anti-Diabetic Drugs (OADs) Metformin	2 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants	6 participants n=4 Participants
Oral Anti-Diabetic Drugs (OADs) Sulphonylurea	8 participants n=5 Participants	12 participants n=7 Participants	10 participants n=5 Participants	30 participants n=4 Participants
Oral Anti-Diabetic Drugs (OADs) Metformin + Sulphonylurea	224 participants n=5 Participants	227 participants n=7 Participants	221 participants n=5 Participants	672 participants n=4 Participants
Diabetic complication, Retinopathy Yes	43 participants n=5 Participants	45 participants n=7 Participants	34 participants n=5 Participants	122 participants n=4 Participants
Diabetic complication, Retinopathy No	191 participants n=5 Participants	194 participants n=7 Participants	201 participants n=5 Participants	586 participants n=4 Participants
Diabetic complication, Neuropathy Yes	39 participants n=5 Participants	55 participants n=7 Participants	41 participants n=5 Participants	135 participants n=4 Participants
Diabetic complication, Neuropathy No	195 participants n=5 Participants	184 participants n=7 Participants	194 participants n=5 Participants	573 participants n=4 Participants
Diabetic complication, Nephropathy Yes	23 participants n=5 Participants	24 participants n=7 Participants	21 participants n=5 Participants	68 participants n=4 Participants
Diabetic complication, Nephropathy No	211 participants n=5 Participants	215 participants n=7 Participants	214 participants n=5 Participants	640 participants n=4 Participants
Diabetic complication, Macroaniopathy Yes	44 participants n=5 Participants	42 participants n=7 Participants	52 participants n=5 Participants	138 participants n=4 Participants
Diabetic complication, Macroaniopathy No	190 participants n=5 Participants	197 participants n=7 Participants	183 participants n=5 Participants	570 participants n=4 Participants
Duration of diabetes	9 years INTER_QUARTILE_RANGE 5.13 • n=5 Participants	9 years INTER_QUARTILE_RANGE 5.54 • n=7 Participants	9 years INTER_QUARTILE_RANGE 5.23 • n=5 Participants	9 years n=4 Participants
Alcohol	4 units INTER_QUARTILE_RANGE 9.16 • n=5 Participants	5 units INTER_QUARTILE_RANGE 7.88 • n=7 Participants	6 units INTER_QUARTILE_RANGE 9.61 • n=5 Participants	5 units n=4 Participants
Weight	85.52 kg STANDARD_DEVIATION 16.25 • n=5 Participants	84.92 kg STANDARD_DEVIATION 14.43 • n=7 Participants	86.91 kg STANDARD_DEVIATION 16.82 • n=5 Participants	85.8 kg STANDARD_DEVIATION 15.9 • n=4 Participants
Body Mass Index (BMI)	29.82 kg/m^2 STANDARD_DEVIATION 4.59 • n=5 Participants	29.74 kg/m^2 STANDARD_DEVIATION 4.51 • n=7 Participants	30.34 kg/m^2 STANDARD_DEVIATION 4.73 • n=5 Participants	29.8 kg/m^2 STANDARD_DEVIATION 4.6 • n=4 Participants
Waist Men	104 cm STANDARD_DEVIATION 12 • n=5 Participants	102 cm STANDARD_DEVIATION 11 • n=7 Participants	104 cm STANDARD_DEVIATION 12 • n=5 Participants	103 cm STANDARD_DEVIATION 12 • n=4 Participants
Waist Women	97 cm STANDARD_DEVIATION 12 • n=5 Participants	100 cm STANDARD_DEVIATION 11 • n=7 Participants	98 cm STANDARD_DEVIATION 13 • n=5 Participants	98 cm STANDARD_DEVIATION 12 • n=4 Participants
Eight-point Capillary Plasma Glucose Profiles All time pointsexcluding 3 am	196 mg/dL STANDARD_DEVIATION 43 • n=5 Participants	200 mg/dL STANDARD_DEVIATION 49 • n=7 Participants	202 mg/dL STANDARD_DEVIATION 47 • n=5 Participants	200 mg/dL STANDARD_DEVIATION 47 • n=4 Participants
Eight-point Capillary Plasma Glucose Profiles Fasting plasma	171 mg/dL STANDARD_DEVIATION 47 • n=5 Participants	173 mg/dL STANDARD_DEVIATION 49 • n=7 Participants	175 mg/dL STANDARD_DEVIATION 50 • n=5 Participants	173 mg/dL STANDARD_DEVIATION 49 • n=4 Participants
Eight-point Capillary Plasma Glucose Profiles Postprandial	223 mg/dL STANDARD_DEVIATION 50 • n=5 Participants	227 mg/dL STANDARD_DEVIATION 56 • n=7 Participants	229 mg/dL STANDARD_DEVIATION 54 • n=5 Participants	227 mg/dL STANDARD_DEVIATION 54 • n=4 Participants
Eight-point Capillary Plasma Glucose Profiles At 3 am	164 mg/dL STANDARD_DEVIATION 56 • n=5 Participants	164 mg/dL STANDARD_DEVIATION 59 • n=7 Participants	171 mg/dL STANDARD_DEVIATION 58 • n=5 Participants	166 mg/dL STANDARD_DEVIATION 58 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Month 12

Population: 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.

HbA1c values offer evidence of the efficacy and durability of the insulin regimens.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
HbA1c (Glycosylated Haemoglobin) at Month 12 Baseline	8.45 percentage (%) of total haemoglobin Standard Deviation 0.80	8.55 percentage (%) of total haemoglobin Standard Deviation 0.78	8.63 percentage (%) of total haemoglobin Standard Deviation 0.81
HbA1c (Glycosylated Haemoglobin) at Month 12 Month 12	7.64 percentage (%) of total haemoglobin Standard Deviation 0.96	7.20 percentage (%) of total haemoglobin Standard Deviation 1.06	7.33 percentage (%) of total haemoglobin Standard Deviation 0.95

PRIMARY outcome

Timeframe: Baseline, Month 36

HbA1c values offer evidence of the efficacy and durability of the insulin regimens.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
HbA1c (Glycosylated Haemoglobin) at Month 36 Baseline	8.45 percentage (%) of total haemoglobin Standard Deviation 0.80	8.55 percentage (%) of total haemoglobin Standard Deviation 0.78	8.63 percentage (%) of total haemoglobin Standard Deviation 0.81
HbA1c (Glycosylated Haemoglobin) at Month 36 Month 36	7.11 percentage (%) of total haemoglobin Standard Deviation 1.13	7.04 percentage (%) of total haemoglobin Standard Deviation 1.17	7.22 percentage (%) of total haemoglobin Standard Deviation 1.11

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
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% Total participants who achieved target	8.1 percentage of participants	23.9 percentage of participants	17.0 percentage of participants
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% Subset who achieved target, n=18, 50, 39	78.9 percentage of participants	43.9 percentage of participants	52.5 percentage of participants

SECONDARY outcome

Timeframe: Month 36

Percentage of participants who achieved the target (HbA1c below or equal to 6.5%) at Month 36

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Percentage of Participants Achieving a Month 36 Value in HbA1c Below or Equal to 6.5%	43.2 percentage of participants	44.8 percentage of participants	31.9 percentage of participants

SECONDARY outcome

Timeframe: 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%.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
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% All participants, Grade 1	2.0 hypoglycaemic events/participant/year Interval 0.0 to 6.0	8.0 hypoglycaemic events/participant/year Interval 3.0 to 19.2	5.0 hypoglycaemic events/participant/year Interval 1.0 to 11.1
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% All participants, Grade 2	0 hypoglycaemic events/participant/year Interval 0.0 to 2.0	8.0 hypoglycaemic events/participant/year Interval 2.9 to 17.7	3.9 hypoglycaemic events/participant/year Interval 1.0 to 9.0
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% All participants, Grade 3	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0
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% All participants, Grade 2 or 3	0 hypoglycaemic events/participant/year Interval 0.0 to 2.0	8.0 hypoglycaemic events/participant/year Interval 3.0 to 18.0	3.9 hypoglycaemic events/participant/year Interval 1.0 to 9.0
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% Achieved HbA1c target, Grade 1, n=18, 50, 39	3.9 hypoglycaemic events/participant/year Interval 0.0 to 5.2	7.8 hypoglycaemic events/participant/year Interval 2.0 to 21.0	5.4 hypoglycaemic events/participant/year Interval 1.5 to 12.8
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% Achieved HbA1c target, Grade 2, n=18, 50, 39	3.0 hypoglycaemic events/participant/year Interval 0.0 to 4.9	8.0 hypoglycaemic events/participant/year Interval 2.0 to 20.0	4.0 hypoglycaemic events/participant/year Interval 1.5 to 11.4
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% Achieved HbA1c target, Grade 3, n=18, 50, 39	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0
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% Achieved HbA1c target, Grade 2 or 3, n=18, 50, 39	3.0 hypoglycaemic events/participant/year Interval 0.0 to 4.9	8.7 hypoglycaemic events/participant/year Interval 2.9 to 20.0	4.0 hypoglycaemic events/participant/year Interval 1.9 to 11.8

SECONDARY outcome

Timeframe: Month 36

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
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% All participants, Grade 1	2.7 hypoglycaemic events/participant/year Interval 2.3 to 3.0	5.7 hypoglycaemic events/participant/year Interval 4.3 to 7.2	3.8 hypoglycaemic events/participant/year Interval 3.3 to 4.3
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% All participants, Grade 2	1.7 hypoglycaemic events/participant/year Interval 1.3 to 2.0	5.5 hypoglycaemic events/participant/year Interval 4.3 to 6.9	3.0 hypoglycaemic events/participant/year Interval 2.3 to 4.0
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% All participants, Grade 3	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0
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% All participants, Grade 2 or 3	1.7 hypoglycaemic events/participant/year Interval 1.3 to 2.0	5.7 hypoglycaemic events/participant/year Interval 4.3 to 7.0	3.0 hypoglycaemic events/participant/year Interval 2.3 to 4.0
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% Achieved HbA1c target, Grade 1, n=73, 70, 55	3.0 hypoglycaemic events/participant/year Interval 1.7 to 3.7	5.7 hypoglycaemic events/participant/year Interval 3.5 to 7.7	3.0 hypoglycaemic events/participant/year Interval 1.7 to 3.9
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% Achieved HbA1c target, Grade 2, n=73, 70, 55	2.0 hypoglycaemic events/participant/year Interval 1.3 to 2.7	5.3 hypoglycaemic events/participant/year Interval 3.8 to 8.0	2.7 hypoglycaemic events/participant/year Interval 1.7 to 5.2
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% Achieved HbA1c target, Grade 3, n=73, 70, 55	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0	0 hypoglycaemic events/participant/year Interval 0.0 to 0.0
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% Achieved HbA1c target, Grade 2 or 3, n=73, 70, 55	2.0 hypoglycaemic events/participant/year Interval 1.3 to 2.7	5.5 hypoglycaemic events/participant/year Interval 4.0 to 8.0	3.0 hypoglycaemic events/participant/year Interval 1.7 to 5.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Percentage of Participants Who Required A Second Insulin Therapy by Month 12	17.9 percentage of participants	4.2 percentage of participants	8.9 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Percentage of Participants Who Required A Second Insulin Therapy by Month 36	89 percentage of participants	82 percentage of participants	88 percentage of participants

SECONDARY outcome

Timeframe: Week 0 (baseline), month 12

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Change From Baseline in Body Weight at Month 12	1.9 kilogram Standard Deviation 4.2	5.7 kilogram Standard Deviation 4.6	4.7 kilogram Standard Deviation 4.0

SECONDARY outcome

Timeframe: Week 0 (baseline), month 36

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Change From Baseline in Body Weight at Month 36	3.6 kilograms Standard Deviation 0.5	6.4 kilograms Standard Deviation 0.5	5.7 kilograms Standard Deviation 0.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months All timepoints excluding 3am	-43 mg/dL Standard Deviation 43	-65 mg/dL Standard Deviation 43	-59 mg/dL Standard Deviation 54
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months Fasting	-59 mg/dL Standard Deviation 52	-23 mg/dL Standard Deviation 49	-45 mg/dL Standard Deviation 56
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months Postprandial	-47 mg/dL Standard Deviation 54	-83 mg/dL Standard Deviation 54	-68 mg/dL Standard Deviation 63
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 Months 3am	-40 mg/dL Standard Deviation 70	-34 mg/dL Standard Deviation 59	-52 mg/dL Standard Deviation 70

SECONDARY outcome

Timeframe: Baseline, month 36

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months All timepoints excluding 3am	-58 mg/dL Standard Deviation 43	-67 mg/dL Standard Deviation 47	-56 mg/dL Standard Deviation 47
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months Fasting	-47 mg/dL Standard Deviation 49	-49 mg/dL Standard Deviation 45	-50 mg/dL Standard Deviation 47
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months Postprandial	-67 mg/dL Standard Deviation 50	-85 mg/dL Standard Deviation 59	-61 mg/dL Standard Deviation 58
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 36 Months 3am	-45 mg/dL Standard Deviation 77	-27 mg/dL Standard Deviation 70	-38 mg/dL Standard Deviation 77

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 12 Months	0.78 units on a scale Interval 0.75 to 0.81	0.76 units on a scale Interval 0.73 to 0.79	0.76 units on a scale Interval 0.73 to 0.8

SECONDARY outcome

Timeframe: Month 36

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Quality of Life as Measured by the EuroQol Group 5-Dimension Self-Report Questionnaire Score (EQ5D) at 36 Months	0.80 units on a scale Interval 0.77 to 0.83	0.77 units on a scale Interval 0.73 to 0.81	0.76 units on a scale Interval 0.71 to 0.8

SECONDARY outcome

Timeframe: Up to month 37 (36 months of treatment plus 1 month follow-up)

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

Outcome measures

Outcome measures
Measure	Insulin Detemir (Basal Insulin) n=234 Participants 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	Insulin Aspart (Prandial Insulin) n=239 Participants 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	Biphasic Insulin Aspart 30 (Biphasic Insulin) n=235 Participants 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
Number of Participants Having an 'Other' Adverse Event	227 participants	235 participants	228 participants

Adverse Events

Insulin Detemir (Basal Insulin)

Serious events: 78 serious events

Other events: 227 other events

Deaths: 0 deaths

Insulin Aspart (Prandial Insulin)

Serious events: 79 serious events

Other events: 235 other events

Deaths: 0 deaths

Biphasic Insulin Aspart 30 (Biphasic Insulin)

Serious events: 105 serious events

Other events: 228 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER