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

Phase 3
Completed
Conditions
Diabetes
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT00184600
Lead Sponsor
Novo Nordisk A/S
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
708
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Insulin aspart (prandial insulin)biphasic insulin aspartIndividually 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.
Biphasic insulin aspart 30 (biphasic insulin)insulin aspartIndividually 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.
Insulin detemir (basal insulin)insulin detemirIndividually 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.
Primary Outcome Measures
NameTimeMethod
HbA1c (Glycosylated Haemoglobin) at Month 12Baseline, Month 12

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

HbA1c (Glycosylated Haemoglobin) at Month 36Baseline, Month 36

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

Secondary Outcome Measures
NameTimeMethod
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.

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 12Month 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 36Month 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.

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%.

Change From Baseline in Body Weight at Month 12Week 0 (baseline), month 12
Change From Baseline in Body Weight at Month 36Week 0 (baseline), month 36
Change in Eight-point Capillary Plasma Glucose Profiles (Self-measured) at 12 MonthsBaseline, 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 MonthsBaseline, 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 MonthsMonth 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 MonthsMonth 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 EventUp to month 37 (36 months of treatment plus 1 month follow-up)

Trial Locations

Locations (1)

Novo Nordisk Investigational Site

🇬🇧

Wirral, Merseyside, United Kingdom

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