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

Phase 4
Completed
Conditions
Diabetes
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT00795600
Lead Sponsor
Novo Nordisk A/S
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
insulin NPHinsulin NPHInsulin 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
insulin detemirinsulin detemirInsulin detemir injected subcutaneously (s.c.) in the evening in combination with insulin aspart injected s.c. as mealtime insulin for 26 weeks
Primary Outcome Measures
NameTimeMethod
Percentage Change in Trunk Fat Mass (Defined as Peripheral Fat Ratio)week 0, week 26

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.

Absolute Change in Trunk Fat Massweek 0, week 26

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.

Secondary Outcome Measures
NameTimeMethod
Absolute Change in AlbuminWeek 0, week 26
Percentage Change in Whole Body Fat MassWeek 0, week 26

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.

Absolute Change in Calculated Whole Body Fat PercentageWeek 0, week 26

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

Absolute Change in Calculated Visceral/Subcutaneous Adipose Tissue RatioWeek 0, week 26

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.

Absolute Change in Low Density Lipoprotein (LDL) CholesterolWeek 0, week 26
Absolute Change in ThrombocytesWeek 0, week 26
Absolute Change in LymphocytesWeek 0, week 26
Absolute Change in NeutrophilsWeek 0, week 26
Absolute Change in Trunk Lean MassWeek 0, week 26

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

Percentual Change in Calculated Trunk Fat PercentageWeek 0, week 26

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.

Percentage Change in Trunk Lean MassWeek 0, week 26

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.

Absolute Change in Whole Body Fat MassWeek 0, week 26

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.

Absolute Change in Whole Body Lean MassWeek 0, week 26

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.

Percentual Change in Calculated Whole Body Fat PercentageWeek 0, week 26

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.

Absolute Change in Calculated Trunk Fat PercentageWeek 0, week 26

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

Percentage Change in Calculated Visceral/Subcutaneous Adipose Tissue RatioWeek 0, week 26

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.

Absolute Change in Free Fatty AcidsWeek 0, week 26
Percentage Change in Whole Body Lean MassWeek 0, week 26

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.

Absolute Change in Visceral Adipose Tissue AreaWeek 0, week 26

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

Absolute Change in Subcutaneous Adipose Tissue AreaWeek 0, week 26

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

Absolute Change in AdiponectinWeek 0, week 26

Absolute change in adiponectin as response variable with treatment, sex and Metformin use as fixed factors, and Adiponectic at week 0 as covariate.

Absolute Change in Total CholesterolWeek 0, week 26
Absolute Change in Blood Volume (Haematocrit)Week 0, week 26
Absolute Change in Creatine PhosphokinaseWeek 0, week 26
Absolute Change in UreaWeek 0, week 26
Absolute Change in HaemoglobinWeek 0, week 26
Percentage Change in Visceral Adipose Tissue AreaWeek 0, week 26

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.

Percentage Change in Subcutaneous Adipose Tissue AreaWeek 0, week 26

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.

Absolute Change in Liver/Spleen Attenuation RatioWeek 0, week 26

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.

Percentage Change in Liver/Spleen Attenuation RatioWeek 0, week 26

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.

Absolute Change in HbA1c (Glycosylated Haemoglobin)Week 0, week 26

Absolute Change in HbA1c as response variable with treatment, sex and Metformin use as fixed factors, and HbA1c at week 0 as covariate.

Absolute Change in EosinophilsWeek 0, week 26
Absolute Change in BasophilsWeek 0, week 26
Absolute Change in CreatinineWeek 0, week 26
Absolute Change in Alanine Aminotransferase (ALAT)Week 0, week 26
Absolute Change in Waist CircumferenceWeek 0, week 26

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.

Absolute Change in Hip CircumferenceWeek 0, week 26

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.

Absolute Change in PAI-1 (Plasminogen Activator Inhibitor-1)Week 0, week 26
Absolute Change in Fasting Plasma Glucose (FPG)Week 0, week 26

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.

Absolute Change in High Density Lipoprotein (HDL) CholesterolWeek 0, week 26
Absolute Change in Very Low Density Lipoprotein (VLDL) CholesterolWeek 0, week 26
Absolute Change in TriglyceridesWeek 0, week 26
Absolute Change in ErythrocytesWeek 0, week 26
Absolute Change in LeucocytesWeek 0, week 26
Absolute Change in MonocytesWeek 0, week 26
Absolute Change in Bilirubin TotalWeek 0, week 26
Absolute Change in Alkaline PhosphataseWeek 0, week 26
Absolute Change in SodiumWeek 0, week 26
Absolute Change in hsCRP (Highly Sensitive C Reactive Protein)Week 0, week 26

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.

Number of Hypoglycaemic EpisodesWeeks 0-26

Number of episodes reported during the trial.

Absolute Change in Aspartate Aminotransferase (ASAT)Week 0, week 26
Absolute Change in PotassiumWeek 0, week 26
Absolute Change in Body WeightWeek 0, week 26

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.

Number of Non-serious Adverse EventsWeeks 0-26

Number of episodes reported during the trial.

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