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.

Objective To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. Design and setting Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. Participants and interventions Participants with type 2 diabetes (glycated haemoglobin (HbA 1c )≥7.5% (≥58 mmol/mol), body mass index >25 kg/m 2 ) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1–3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA 1c ≤7.0% (≤53 mmol/mol). Outcomes Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA 1c , insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes. Results 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)). HbA 1c was more reduced with biphasic (−1.0% (95% CI −1.2 to −0.8)) compared with the aspart+detemir (−0.4% (95% CI −0.6 to −0.3)) and detemir (−0.3% (95% CI −0.4 to −0.1)) groups (p Conclusions Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA 1c , weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results. Trial registration number NCT00657943.