Comparison of the Change in Fat Distribution in Overweight and Obese Subjects With Type 2 Diabetes After Insulin Treatment

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this clinical trial is to compare the change in trunk fat mass, assessed by Double Energy X-ray Absorptiometry (DEXA) after 26 weeks of treatment with insulin detemir or insulin NPH (Neutral Protamine Hagedorn) (both combined with insulin aspart at the main meals) in overweight and obese subjects with type 2 diabetes.

Official Title
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A Multi-centre, Open-labelled, Randomised, Two-group Parallel Trial Comparing the Change in Fat Distribution in Overweight and Obese Subjects With Type 2 Diabetes After 26 Weeks of Treatment With Insulin Detemir Once Daily Versus Insulin NPH Once Daily, Both With Insulin Aspart at Mealtimes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: insulin detemir
* Drug: insulin NPH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with type 2 diabetes who have been treated with 2 or 3 doses of insulin (one of them must be a premix) for at least 3 months prior to inclusion in trial Glycosylated haemoglobin (HbA1c) between 7.0-11.0 % Body Mass Index (BMI) between 27.5-40 kg/m^2 Exclusion Criteria: Treatment with any oral antidiabetic drugs (OADs) in the last 6 months except metformin (subjects currently treated with metformin within the interval of 1000 - 2550 mg daily may be included in the trial. The dose should have remained unchanged for a period of 2 months prior to randomisation and should be expected to remain unchanged throughout the trial period) Use of approved weight lowering pharmacotherapy (e.g. orlistat, sibutramin, rimonabant) or obesity induced by drug treatment (e.g. corticosteroids, Non-steroidal anti-inflammatory drugs (NSAIDs), tricyclic anti-depressants, atypical anti-psychotics) Previous or planned surgical treatment of obesity Total daily insulin dose higher or equal 2 IU/kg Proliferative retinopathy or maculopathy that has required acute treatment within the last six months Receipt of any investigational drug within 1 month prior to this trial Cardiac disease defined according to New York Heart Association (NYHA) class III or IV, unstable angina pectoris and/or myocardial infarction within the last 6 months previous to the selection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: insulin detemir<br>Insulin detemir injected subcutaneously (s.c.) in the evening in combination with insulin aspart injected s.c. as mealtime insulin for 26 weeks | Drug: insulin detemir<br>* Insulin detemir once daily plus insulin aspart at mealtime<br>|
| Active Comparator: insulin NPH<br>Insulin isophane (Neutral Protamine Hagedorn, NPH) injected subcutaneously (s.c.) in the evening in combination with insulin aspart injected s.c. as mealtime insulin for 26 weeks | Drug: insulin NPH<br>* Insulin NPH once daily plus insulin aspart at mealtime<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Trunk Fat Mass (Defined as Peripheral Fat Ratio) | Percentage of change of trunk fat mass as the dependent variable, baseline value (trunk fat mass at week 0) as covariate, treatment with metformin (yes/no) and gender (male/female) as effect and the treatment received (insulin detemir/insulin NPH) as the main factor. | week 0, week 26 | 
| Absolute Change in Trunk Fat Mass | Absolute change in trunk fat mass as response variable with treatment, sex and Metformin use as fixed factors, and trunk fat mass at week 0 as covariate. | week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Whole Body Fat Mass | Absolute change in whole body fat mass as response variable with treatment, sex and Metformin use as fixed factors, and trunk fat mass at week 0 as covariate. | Week 0, week 26 | 
| Percentage Change in Whole Body Fat Mass | Percentage Change in Whole Body Fat Mass as response variable with treatment, sex and Metformin use as fixed factors, and whole Body Fat Mass at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Whole Body Lean Mass | Absolute change in whole body lean mass as response variable with treatment, sex and Metformin use as fixed factors, whole body lean mass at week 0 as covariate. | Week 0, week 26 | 
| Percentage Change in Whole Body Lean Mass | Percentage Change in Whole Body Lean Mass as response variable with treatment, sex and Metformin use as fixed factors, and whole Body Lean Mass at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Trunk Lean Mass | Absolute change in trunk lean mass as response variable with treatment, sex and Metformin use as fixed factors, and trunk lean mass at week 0 as covariate | Week 0, week 26 | 
| Percentage Change in Trunk Lean Mass | Percentage Change in Trunk Lean Mass as response variable with treatment, sex and Metformin use as fixed factors, and Trunk Lean Mass at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Calculated Whole Body Fat Percentage | Absolute change in calculated whole body fat percentage as response variable with treatment, sex and Metformin use as fixed factors, and calculated whole body fat percentage at week 0 as covariate | Week 0, week 26 | 
| Percentual Change in Calculated Whole Body Fat Percentage | Percentual Change in Calculated Whole Body Fat Percentage as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Whole Body Fat Percentage at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Calculated Trunk Fat Percentage | Absolute change in calculated trunk fat percentage as response variable with treatment, sex and Metformin use as fixed factors, and calculated trunk fat percentage at week 0 as covariate | Week 0, week 26 | 
| Percentual Change in Calculated Trunk Fat Percentage | Percentual Change in Calculated Trunk Fat Percentage as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Trunk Fat Percentage at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Visceral Adipose Tissue Area | Absolute change in visceral adipose tissue area as response variable with treatment, sex and Metformin use as fixed factors, and visceral adipose tissue area at week 0 as covariate | Week 0, week 26 | 
| Percentage Change in Visceral Adipose Tissue Area | Percentage Change in Visceral Adipose Tissue Area as response variable with treatment, sex and Metformin use as fixed factors, and Visceral Adipose Tissue Area at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Subcutaneous Adipose Tissue Area | Absolute change in subcutaneous adipose tissue area as response variable with treatment, sex and Metformin use as fixed factors, and subcutaneous adipose tissue area at week 0 as covariate | Week 0, week 26 | 
| Percentage Change in Subcutaneous Adipose Tissue Area | Percentage Change in Subcutaneous Adipose Tissue Area as response variable with treatment, sex and Metformin use as fixed factors, and Subcutaneous Adipose Tissue Area at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Calculated Visceral/Subcutaneous Adipose Tissue Ratio | Absolute change in Calculated Visceral/Subcutaneous Adipose Tissue Ratio as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Visceral/Subcutaneous Adipose Tissue Area at week 0 as covariate. | Week 0, week 26 | 
| Percentage Change in Calculated Visceral/Subcutaneous Adipose Tissue Ratio | Percentage Change in Calculated Visceral/Subcutaneous Adipose Tissue Area as response variable with treatment, sex and Metformin use as fixed factors, and Calculated Visceral/Subcutaneous Adipose Tissue Area at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Liver/Spleen Attenuation Ratio | Absolute change in Liver/Spleen Attenuation Ratio as response variable with treatment, sex and Metformin use as fixed factors, and Liver/Spleen Attenuation Ratio at week 0 as covariate. | Week 0, week 26 | 
| Percentage Change in Liver/Spleen Attenuation Ratio | Percentage Change in Liver/Spleen Attenuation Ratio as response variable with treatment, sex and Metformin use as fixed factors, and Liver to Spleen Attenuation Ratio at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in HbA1c (Glycosylated Haemoglobin) | Absolute Change in HbA1c as response variable with treatment, sex and Metformin use as fixed factors, and HbA1c at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Fasting Plasma Glucose (FPG) | Absolute Change in Fasting Plasma Glucose as response variable with treatment, sex and Metformin use as fixed factors, and Fasting Plasma Glucose at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Adiponectin | Absolute change in adiponectin as response variable with treatment, sex and Metformin use as fixed factors, and Adiponectic at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Total Cholesterol |  | Week 0, week 26 | 
| Absolute Change in High Density Lipoprotein (HDL) Cholesterol |  | Week 0, week 26 | 
| Absolute Change in Low Density Lipoprotein (LDL) Cholesterol |  | Week 0, week 26 | 
| Absolute Change in Very Low Density Lipoprotein (VLDL) Cholesterol |  | Week 0, week 26 | 
| Absolute Change in Triglycerides |  | Week 0, week 26 | 
| Absolute Change in Free Fatty Acids |  | Week 0, week 26 | 
| Absolute Change in Haemoglobin |  | Week 0, week 26 | 
| Absolute Change in Blood Volume (Haematocrit) |  | Week 0, week 26 | 
| Absolute Change in Thrombocytes |  | Week 0, week 26 | 
| Absolute Change in Erythrocytes |  | Week 0, week 26 | 
| Absolute Change in Leucocytes |  | Week 0, week 26 | 
| Absolute Change in Lymphocytes |  | Week 0, week 26 | 
| Absolute Change in Monocytes |  | Week 0, week 26 | 
| Absolute Change in Neutrophils |  | Week 0, week 26 | 
| Absolute Change in Eosinophils |  | Week 0, week 26 | 
| Absolute Change in Basophils |  | Week 0, week 26 | 
| Absolute Change in Creatinine |  | Week 0, week 26 | 
| Absolute Change in Creatine Phosphokinase |  | Week 0, week 26 | 
| Absolute Change in Urea |  | Week 0, week 26 | 
| Absolute Change in Albumin |  | Week 0, week 26 | 
| Absolute Change in Bilirubin Total |  | Week 0, week 26 | 
| Absolute Change in Alanine Aminotransferase (ALAT) |  | Week 0, week 26 | 
| Absolute Change in Aspartate Aminotransferase (ASAT) |  | Week 0, week 26 | 
| Absolute Change in Alkaline Phosphatase |  | Week 0, week 26 | 
| Absolute Change in Sodium |  | Week 0, week 26 | 
| Absolute Change in Potassium |  | Week 0, week 26 | 
| Absolute Change in Body Weight | Absolute change in body weight was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex and Metformin use as fixed factors, and body weight at week 0 as covariable. | Week 0, week 26 | 
| Absolute Change in Waist Circumference | Absolute change in waist circumference was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex and Metformin use as fixed factors, and Waist at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in Hip Circumference | Absolute Change in Hip Circumferences was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex, and Metformin use as fixed factors, and hip circumference at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in hsCRP (Highly Sensitive C Reactive Protein) | Absolute change in hsCRP was based on ANCOVA model for absolute change from week 0 to week 26 as response variable with treatment, sex and Metformin use as fixed factors, and hsCRP at week 0 as covariate. | Week 0, week 26 | 
| Absolute Change in PAI-1 (Plasminogen Activator Inhibitor-1) |  | Week 0, week 26 | 
| Number of Hypoglycaemic Episodes | Number of episodes reported during the trial. | Weeks 0-26 | 
| Number of Non-serious Adverse Events | Number of episodes reported during the trial. | Weeks 0-26 |