The Copenhagen Insulin and Metformin Therapy Trial

Study Overview
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Brief Summary
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Type 2 Diabetes Mellitus patients (T2DM) have an increased mortality rate due to macrovascular disease. The primary objective of the study is to evaluate the effect of an 18-month treatment with metformin versus placebo in combination with one of three insulin analogue regimens following a treat-to-target principle. The primary outcome measure is change in wall thickness of the carotic arteries(CIMT)measured by ultrasound. A total of 900 patients with T2DM and HbA1c above 7.5% will be included.

Official Title
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The Effect of Metformin Versus Placebo, Including Three Insulin-Analogue Regimens With Variating Postprandial Glucose Regulation, on CIMT in T2DM Patients - A Randomized, Multicenter Trial

Conditions
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Type 2 Diabetes, Atherosclerosis, Arteriosclerosis

Intervention / Treatment
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* Drug: metformin
* Drug: insulin detemir
* Drug: insulin aspart + insulin aspart protamin
* Drug: Insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females over 30 years of age Type 2 diabetes Body mass index (BMI): 25.0-39.9 kg/m2 HbA1c above 7.5 % Antidiabetic tablet-treatment during 1 year minimum AND / OR Insulin treatment during a minimum of 3 months Negative pregnancy test Signed, informed consent Exclusion Criteria: MI, coronary revascularization, TCI,or apoplexy within the last 3 months TCI with verified stenosis of above 70% Heart failure (NYHA class III or IV) Former cancer patient, unless disease-free period of more than 5 years estimated creatinine clearance < 60 ml/min Liver disease Alcohol abuse Drug abuse Retinopathy with on-going laser treatment at start of study Other acute or chronic serious disease leading to hypoxia Pregnant or breastfeeding women Women of child-bearing potential, not using contraceptives Allergy to medication used in the study Incapable of understanding the nature of the informed consent

Ages Eligible for Study
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Minimum Age: 30 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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1M<br>Metformin + Levemir x1 | Drug: metformin<br>* metformin tablets 2 g x 2<br>* Other names: glucophage;Drug: insulin detemir<br>* insulin as requested<br>* Other names: Levemir;|
| Placebo Comparator: 1P<br>Placebo + Levemir x1 | Drug: insulin detemir<br>* insulin as requested<br>* Other names: Levemir;|
| Experimental: 2M<br>metformin + NovoMix | Drug: metformin<br>* metformin tablets 2 g x 2<br>* Other names: glucophage;Drug: insulin aspart + insulin aspart protamin<br>* insulin as requested<br>* Other names: novomix;|
| Placebo Comparator: 2P<br>Placebo + NovoMix | Drug: insulin aspart + insulin aspart protamin<br>* insulin as requested<br>* Other names: novomix;|
| Experimental: 3M<br>Metformin + 4x therapy | Drug: metformin<br>* metformin tablets 2 g x 2<br>* Other names: glucophage;Drug: insulin detemir<br>* insulin as requested<br>* Other names: Levemir;Drug: Insulin aspart<br>* insulin as requested<br>* Other names: NovoRapid;|
| Placebo Comparator: 3P<br>Placebo + 4x therapy | Drug: insulin detemir<br>* insulin as requested<br>* Other names: Levemir;Drug: Insulin aspart<br>* insulin as requested<br>* Other names: NovoRapid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid intima media thickness |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carotid, intima, media, thickness, insulin, metformin