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 (HbA1c)≥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 HbA1c≤7.0% (≤53 mmol/mol).OUTCOMES: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, 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)). HbA1c 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 (pCONCLUSIONS: Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA1c, 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.