The Copenhagen Insulin and Metformin Therapy Trial

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

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.

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