Clinical trial NCT00657943: The Copenhagen Insulin and Metformin Therapy Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Atherosclerosis
Arteriosclerosis
Keywords: carotid
intima
media
thickness
insulin
metformin
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Hvidovre University Hospital
name: Hillerod Hospital, Denmark
name: Frederiksberg University Hospital
name: University Hospital, Gentofte, Copenhagen
name: Rigshospitalet, Denmark
name: Bispebjerg Hospital
name: Herlev Hospital
name: Zealand University Hospital
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
name: Novo Nordisk A/S
First posted: 2008-04-14
Enrollment: 415
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Carotid intima media thickness
timeFrame: 18 months
Secondary outcomes:
measure: adverse events
timeFrame: 18 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Frederiksberg
country: Denmark
facility: Frederiksberg Hospital
city: Gentofte
country: Denmark
facility: Gentofte Sygehus
city: Gentofte
country: Denmark
facility: Steno Diabetes Center
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Hillerod
country: Denmark
facility: Hillerod Sygehus
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Koge
country: Denmark
facility: Køge Sygehus
Study officials:
affiliation: Hvidovre University Hospital
name: Thomas Almdal, MD DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hansen CS, Lundby-Christiansen L, Tarnow L, Gluud C, Hedetoft C, Thorsteinsson B, Hemmingsen B, Wiinberg N, Sneppen SB, Lund SS, Krarup T, Madsbad S, Almdal T, Carstensen B, Jorgensen ME; CIMT study group. Metformin may adversely affect orthostatic blood pressure recovery in patients with type 2 diabetes: substudy from the placebo-controlled Copenhagen Insulin and Metformin Therapy (CIMT) trial. Cardiovasc Diabetol. 2020 Sep 26;19(1):150. doi: 10.1186/s12933-020-01131-3.
citation: Nordklint AK, Almdal TP, Vestergaard P, Lundby-Christensen L, Boesgaard TW, Breum L, Gade-Rasmussen B, Sneppen SB, Gluud C, Hemmingsen B, Jensen T, Krarup T, Madsbad S, Mathiesen ER, Perrild H, Tarnow L, Thorsteinsson B, Vestergaard H, Lund SS, Eiken P. The effect of metformin versus placebo in combination with insulin analogues on bone mineral density and trabecular bone score in patients with type 2 diabetes mellitus: a randomized placebo-controlled trial. Osteoporos Int. 2018 Nov;29(11):2517-2526. doi: 10.1007/s00198-018-4637-z. Epub 2018 Jul 19.
citation: Lundby-Christensen L, Vaag A, Tarnow L, Almdal TP, Lund SS, Wetterslev J, Gluud C, Boesgaard TW, Wiinberg N, Perrild H, Krarup T, Snorgaard O, Gade-Rasmussen B, Thorsteinsson B, Roder M, Mathiesen ER, Jensen T, Vestergaard H, Hedetoft C, Breum L, Duun E, Sneppen SB, Pedersen O, Hemmingsen B, Carstensen B, Madsbad S. Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial. BMJ Open. 2016 Feb 25;6(2):e008377. doi: 10.1136/bmjopen-2015-008377.
citation: Lundby-Christensen L, Tarnow L, Boesgaard TW, Lund SS, Wiinberg N, Perrild H, Krarup T, Snorgaard O, Gade-Rasmussen B, Thorsteinsson B, Roder M, Mathiesen ER, Jensen T, Vestergaard H, Hedetoft C, Breum L, Duun E, Sneppen SB, Pedersen O, Hemmingsen B, Carstensen B, Madsbad S, Gluud C, Wetterslev J, Vaag A, Almdal TP. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial. BMJ Open. 2016 Feb 25;6(2):e008376. doi: 10.1136/bmjopen-2015-008376.