The Copenhagen Insulin and Metformin Therapy Trial
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.
Timeline
- Start
- 2008-04
- Primary completion
- 2012-12
- Completion
- 2012-12
Outcome
Missed primary endpoint
paper Change in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI -0.003 to 0.026), p=0.11). PMID 26916684 ↗
paper Carotid IMT change did not differ between groups (biphasic -0.009 mm (95% CI -0.022 to 0.004), aspart+detemir 0.000 mm (95% CI -0.013 to 0.013), detemir -0.012 mm (95% CI -0.025 to 0.000)). PMID 26916685 ↗
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Metformin | Small molecule | 2 g | — |
| Subject | insulin aspart | Protein / enzyme biologic | — | — |
| Subject | insulin aspart protamin | Unknown | — | — |
| Subject | insulin detemir | Protein / enzyme biologic | — | — |