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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: insulin detemir; Drug: insulin NPH

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Málaga, Spain, 29009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: insulin detemir; 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; Insulin detemir once daily plus insulin aspart at mealtime
ACTIVE_COMPARATOR: insulin NPH; 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; Insulin NPH once daily plus insulin aspart at mealtime

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD005613. doi: 10.1002/14651858.CD005613.pub4.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: November 20, 2008
• First Submitted That Met QC Criteria: November 20, 2008
• First Posted (ESTIMATE): November 21, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 16, 2016
• Last Update Submitted That Met QC Criteria: February 18, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Detemir; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: NN304-3614; 2008-003739-19 (EUDRACT_NUMBER)