Study on Liver Fat Content and Visceral Fat Mass in Overweight and Obese Type 2 Diabetes Patients After Treatment With Basal Insulin

Study Overview
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Brief Summary
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Primary objective: To compare the change in liver fat content and visceral fat mass (cm2) assessed by MRS (Magnetic Resonance Spectroscopy) and MRI (Magnetic Resonance Image), after 26 weeks of treatment with insulin detemir once daily or insulin NPH once daily both with metformin in overweight and obese type 2 diabetic subjects. Secondary objectives: To compare the two treatments with respect to: Efficacy: MRI: abdominal subcutaneous fat mass(cm2), Calculated Visceral/Subcutaneous Adipose Tissue Ratio. Change in HbA1c from baseline at 12 and 26 weeks of treatment. Change in Fasting plasma glucose from baseline at 12 and 26 weeks of treatment. Weight Waist and hip circumference Safety: Incidence of hypoglycaemia in the 26 weeks of treatment with insulin detemir versus NPH Lipid profile at the start and after 26 weeks of treatment Incidence of Adverse events during the trial Safety profile as measured by laboratory safety parameters (haematology, biochemistry) and physical examination/vital signs before and at the end of treatment

Official Title
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A Multi-centre, Open-labeled, Randomized, Parallel Study on Liver Fat Content and Visceral Fat Mass in Overweight and Obese Type 2 Diabetes Patients After 26 Weeks Treatment With Insulin Detemir Once Daily Versus Insulin NPH Once Daily

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: insulin detemir
* Drug: neutral protamine insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) Female or male, 18 years≤age≤70years Subjects with insulin naïve type 2 diabetes who have been treated with metformin（>1g/d）alone for at least 3 months prior to screening 11%≥HbA1c≥7.5% based on analysis from a central laboratory 24kg/m2≤BMI≤40kg/m2 Weight fluctuation<2kg in one month prior to screening Able and willing to perform self-monitoring of blood glucose. Willing to accept basal insulin therapy Able to self-inject all required doses of insulin Exclusion Criteria: Treatment with any OADs (Oral Antidiabetic Drugs) in the last 6 months, except metformin (subjects currently treated with metformin within the interval of 1000-2000 mg daily may be included in the trial. The dose should have remained unchanged for a period of one month prior to randomisation and should be expected to remain unchanged throughout the trial period). Use of approved weight lowering pharmacotherapy (e.g. orlistat, sibutramine, rimonabant) or obesity induced by drug treatment (e.g. corticosteroids, NSAIDs, tricyclic anti-depressants, atypical anti-psychotics). Participation in a clinical study of weight control within the last 3 months prior to screening. Previous or planned surgical treatment of obesity. Any disease or condition (such as renal, hepatic or cardiac) according to the judgment of the Investigator makes the subject unsuitable for participation in the trial. Anticipated change in concomitant medication known to interfere with glucose metabolism, such as systemic steroids, non-selective beta-blockers or mono amine oxidase (MAO) inhibitors. Anticipated change in concomitant medication known to interfere with lipid metabolism, such as lipid-lowering drugs. Proliferative retinopathy or maculopathy that has required acute treatment within the last six months. Uncontrolled hypertension (treated or untreated) as judged by the Investigator Known or suspected allergy to trial product(s) or related products. Previous participation in this trial. Participation is defined as screened. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures. Adequate contraceptive measures are sterilisation, intrauterine device (IUD), oral contraceptives or consistent use of barrier methods. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation. Any condition that the Investigator feels would interfere with trial participation or evaluation of results. Receipt of any investigational drug (NPH or insulin detemir) within 1 month prior to this trial. Cardiac disease defined according to NYHA class III or IV, unstable angina pectoris and/or myocardial infarction within the last 6 months previous to the selection. History of hypoglycaemic unawareness. With mental implant (such as cardiac pacemaker, insulin pump) in vivo.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: neutral protamine insulin, metformin<br>NPH insulin once daily plus oral metformin twice or thrice daily during 26 weeks | Drug: insulin detemir<br>* insulin detemir once daily with metformin<br>|
| Experimental: insulin detemir, metformin<br>Insulin detemir once daily plus oral metformin twice or thrice daily during 26 weeks | Drug: neutral protamine insulin<br>* neutral protamine insulin once daily with metformin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in liver fat content and visceral fat mass | To compare the change in liver fat content and visceral fat mass (cm2), assessed by MRS and MRI, after 26 weeks of treatment with insulin detemir or insulin NPH (both with metformin) in overweight and obese type 2 diabetic subjects | After 26 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI | Abdominal subcutaneous fat mass(cm2), Calculated Visceral/Subcutaneous Adipose Tissue Ratio. | after 26 weeks of treatment | 
| Change in HbA1c | Change in HbA1c from baseline at 12 and 26 weeks of treatment respectively | from baseline to 12 and 26 weeks of treatment respectively | 
| Change in Fasting plasma glucose | Change in Fasting plasma glucose (FPG) from baseline at 12 and 26 weeks of treatment respectively | From baseline to 12 and 26 weeks | 
| Weight at every visit | Weight at every visit | At every visit | 
| Waist and hip circumference at every visit | Waist and hip circumference at every visit | At every visit | 
| Hypoglycaemia | Incidence of hypoglycaemia in the 26 weeks of treatment with insulin detemir versus NPH | during the 26-week treatment | 
| Lipid profile | Lipid profile at the start and after 26 weeks of treatment | At the start and after 26 weeks of treatment | 
| Adverse events | Incidence of Adverse events during the trial | During the trial | 
| Safety profile | Safety profile as measured by laboratory safety parameters (haematology, biochemistry) and physical examination/vital signs before and at the end of treatment | During the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, basal insulin, metformin, liver fat, visceral fat