TY - JOUR
T1 - Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus
T2 - the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
AU - Lundby-Christensen, Louise
AU - Vaag, Allan
AU - Tarnow, Lise
AU - Almdal, Thomas P
AU - Lund, Søren S
AU - Wetterslev, Jørn
AU - Gluud, Christian
AU - Boesgaard, Trine W
AU - Wiinberg, Niels
AU - Perrild, Hans
AU - Krarup, Thure
AU - Snorgaard, Ole
AU - Gade-Rasmussen, Birthe
AU - Thorsteinsson, Birger
AU - Røder, Michael
AU - Mathiesen, Elisabeth R
AU - Jensen, Tonny
AU - Vestergaard, Henrik
AU - Hedetoft, Christoffer
AU - Breum, Leif
AU - Duun, Elsebeth
AU - Sneppen, Simone B
AU - Pedersen, Oluf
AU - Hemmingsen, Bianca
AU - Carstensen, Bendix
AU - Madsbad, Sten
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
PY - 2016
Y1 - 2016
N2 - 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 (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ.CONCLUSIONS: 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.
AB - 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 (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ.CONCLUSIONS: 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.
U2 - 10.1136/bmjopen-2015-008377
DO - 10.1136/bmjopen-2015-008377
M3 - Journal article
C2 - 26916685
VL - 6
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 2
M1 - e008377
ER -