Study rationale and design of the CIMT trial: The Copenhagen Insulin and Metformin Therapy Trial

Abstract

CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease.

Treat-to-target trials in diabetes

“…[24] In another planned study currently underway, the effect of an 18 m treatment with one of three insulin analogue regimens (1. insulin detemir before bedtime; 2. biphasic insulin aspart 30 before dinner with the possibility to increase to 2/3 injections daily; 3. insulin aspart before the main meals thrice daily and insulin detemir before) and metformin vs. placebo is proposed to be evaluated, the primary outcome measure being carotid intima-medial thickness in T2D patients aiming for an HbA1c ≤7.0%. [23] While, reduction in HbA1c levels is associated with reduced CV risk, the risk of CV aggravation is a persistent factor in the treatment of diabetes patients. [3749] While the central concern of glycemic control and CV risk in diabetes are being addressed separately in clinical trials, treat-to-target trials have the potential to help us understand diabetes comorbidities in a clinical scenario where glycemic targets need primary attention.…”

“…[3749] While the central concern of glycemic control and CV risk in diabetes are being addressed separately in clinical trials, treat-to-target trials have the potential to help us understand diabetes comorbidities in a clinical scenario where glycemic targets need primary attention. [23] Such understanding might go a long way in deciphering new benefits of diabetes treatment or point out hidden dangers, and thus contribute to the use of right options in the right context. Table 2 presents an overview of studies which measured CV and patient satisfaction outcomes.…”

“…Efficacy and safety outcomes have been the main focus but other outcomes relating to treatment satisfaction, health-related quality of life etc., have also been tested. [212223] Pertinent questions such as the initiation of different insulins either singly or in combination with oral anti-hyperglycemic drugs, or their relative safety at a given target, or efficacy in the face of fixed safety targets etc., have been examined. [13] A narrow focus on one target (e.g.…”

Molecular mechanisms of hyperglycemia and cardiovascular-related events in critically ill patients: rationale for the clinical benefits of insulin therapy

“…However, the Copenhagen Insulin and Metformin Therapy (CIMT) trial will measure the change in carotid intima-media thickness, and other cardiovascular variables, following 18 months of treatment with insulins detemir and aspart 50. Carotid intima-media thickness often serves as a proxy for progression of macrovascular disease.…”

“…Carotid intima-media thickness often serves as a proxy for progression of macrovascular disease. The technique involves imaging an arterial wall segment of the common carotid arteries 50. Vehkavaara and Yki-Jarvinen studied the vascular effects of insulin glargine added to metformin in 11 patients whose type 2 diabetes was poorly controlled by metformin monotherapy 51.…”