Comparison of the Blood Sugar Lowering Effect and Safety of Two Insulin Treatments in Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
This trial is conducted in Europe, Africa and the United States of America (USA). The aim of this trial is to compare the safety and efficacy of two different insulin treatments, the basic and the advanced treatment in type 2 diabetes.

Official Title
-----------------
Comparison of the Efficacy and Safety of Step-wise Addition of Short Acting Insulin Analogue Insulin Aspart to Once Daily Insulin Detemir and Oral Anti-diabetic Treatment in Patients With Type 2 Diabetes

Conditions
-----------------
Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: insulin detemir
* Drug: insulin aspart
* Drug: insulin aspart


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes mellitus for more than 6 months HbA1c (glycosylated haemoglobin A1c) between 7.5 % and 10.0% at trial initiation (screening) BMI (Body Mass Index) less than 40 kg/m2 Basal insulin treatment for at least 3 months (NPH once or twice daily, insulin glargine or detemir once daily) Treatment with one to 3 OADs Exclusion Criteria: Known or suspected allergy to trial products or related products Women who are pregnant, are breast-feeding or intend to become pregnant within the next 48 weeks Previous participation in any trial including this for the last 6 months Use of more than 1 U/kg of basal insulin daily at trial initiation (screening)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced<br>Insulin detemir once daily + oral anti-diabetic drugs (OADs) with addition of meal-time insulin aspart stepwise (1-2-3) at the meals with the largest prandial increments and individually adjusted insulin aspart based mainly on postmeal SMPG (self monitored plasma glucose). The stepwise addition occurred if the treatment target of HbA1c below 7.0% was not reached after 12, 24 and 36 weeks, respectively. | Drug: insulin detemir<br>* Treat-to-target dose titration scheme (individually adjusted dose) for a once daily injection s.c. (under the skin)<br>Drug: insulin aspart<br>* Administered 1 - 3 times daily, at largest prandial increment, injection s.c. (under the skin)<br>|
| Active Comparator: Basic<br>Insulin detemir once daily + oral anti-diabetic drugs (OADs) with addition of meal-time insulin aspart stepwise (1-2-3) at the largest meals and individually adjusted insulin aspart based mainly on pre-meal and bedtime SMPG (self monitored plasma glucose). The stepwise addition occurred if the treatment target of HbA1c below 7.0% was not reached after 12, 24 and 36 weeks, respectively. | Drug: insulin detemir<br>* Treat-to-target dose titration scheme (individually adjusted dose) for a once daily injection s.c. (under the skin)<br>Drug: insulin aspart<br>* Administered 1 - 3 times daily, at largest meals, injection s.c. (under the skin)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycosylated Haemoglobin A1c (HbA1c) | Analysed for the full analysis set. | week 36 | 
| Glycosylated Haemoglobin A1c (HbA1c) | Measured for the Per Protocol analysis set. | week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycaemic Episodes | Number of hypoglycaemic episodes from Week 0 to Week 36, defined as major, minor or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L (56 mg/dL). Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. | Weeks 0-36 | 
| Biochemistry: Serum Alanine Aminotransferase | Alanine aminotransferase was measured in serum at week 36. Serum samples were analysed at a central laboratory. | week 36 | 
| Haematology: Haemoglobin Measured in Blood | Haemoglobin was measured in blood samples at week 36. Blood samples were analysed at a central laboratory. | week 36 | 
| Cardiovascular Risk Marker: High-sensitivity C-reactive Peptide | High-sensitivity C-reactive peptide was measured in serum at week 36. Serum samples were analysed at a central laboratory. | week 36 |