The Copenhagen Insulin and Metformin Therapy Trial

NCT00657943 | Completed Phase 4 DMC

• 1 other identifier: EudraCT 2007-006665-33
• Study Type: interventional
• Target: 415
• Locations: 1 country
• Sites: 9

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.

Conditions

Type 2 Diabetes; Atherosclerosis; Arteriosclerosis

Keywords

carotid; intima; media; thickness; insulin; metformin

Outcome Measures

Primary Outcomes (1)

• Carotid intima media thickness

  18 months

Secondary Outcomes (1)

• adverse events

  18 months

Study Arms (6)

1M

EXPERIMENTAL

Metformin + Levemir x1

Drug: metformin; Drug: insulin detemir

1P

PLACEBO COMPARATOR

Placebo + Levemir x1

Drug: insulin detemir

2M

EXPERIMENTAL

metformin + NovoMix

Drug: metformin; Drug: insulin aspart + insulin aspart protamin

2P

PLACEBO COMPARATOR

Placebo + NovoMix

Drug: insulin aspart + insulin aspart protamin

3M

EXPERIMENTAL

Metformin + 4x therapy

Drug: metformin; Drug: insulin detemir; Drug: Insulin aspart

3P

PLACEBO COMPARATOR

Placebo + 4x therapy

Drug: insulin detemir; Drug: Insulin aspart

Interventions

metformin DRUG

metformin tablets 2 g x 2

Also known as: glucophage

1M; 2M; 3M

insulin detemir DRUG

insulin as requested

Also known as: Levemir

1M; 1P; 3M; 3P

insulin aspart + insulin aspart protamin DRUG

insulin as requested

Also known as: novomix

2M; 2P

Insulin aspart DRUG

insulin as requested

Also known as: NovoRapid

3M; 3P

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• Hvidovre University Hospital: collaborator
• Hillerod Hospital, Denmark: collaborator
• Frederiksberg University Hospital: collaborator
• University Hospital, Gentofte, Copenhagen: collaborator
• Rigshospitalet, Denmark: collaborator
• Bispebjerg Hospital: collaborator
• Herlev Hospital: collaborator
• Zealand University Hospital: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (9)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Frederiksberg Hospital

Frederiksberg, 2000, Denmark

Location

Gentofte Sygehus

Gentofte Municipality, 2820, Denmark

Location

Steno Diabetes Center

Gentofte Municipality, 2820, Denmark

Location

Herlev Hospital

Herlev, 2830, Denmark

Location

Hillerod Sygehus

Hillerød, 3400, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Køge Sygehus

Køge, 4600, Denmark

Location

Related Publications (5)

• Olsen MH, Almdal TP, Madsbad S, Ovesen C, Gluud C, Sneppen SB, Breum L, Hedetoft C, Krarup T, Lundby-Christensen L, Mathiesen ER, Roder ME, Vestergaard H, Wiinberg N, Jakobsen JC. Quality of life, patient satisfaction, and cardiovascular outcomes of the randomised 2 x 3 factorial Copenhagen insulin and Metformin therapy (CIMT) trial - A detailed statistical analysis plan. Contemp Clin Trials Commun. 2023 Feb 24;33:101095. doi: 10.1016/j.conctc.2023.101095. eCollection 2023 Jun.

  PMID: 36923108 DERIVED

• 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.

  PMID: 32979921 DERIVED

• 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.

  PMID: 30027438 DERIVED

• 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.

  PMID: 26916685 DERIVED

• 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.

  PMID: 26916684 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Atherosclerosis; Arteriosclerosis; Insulin Resistance

Interventions

Metformin; Insulin Detemir; Insulin Aspart

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Short-Acting

Study Officials

• Thomas Almdal, MD DMSc

  Hvidovre University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 4, 2014

Record last verified: 2014-02

Locations

DK (9)