Key result
Biphasic aspart, aspart plus detemir, and detemir alone show no difference in carotid IMT change.
Why the study?
Does the choice of insulin analogue regimen (biphasic, basal-bolus, or basal) reduce carotid intima-media thickness in patients with type 2 diabetes?
RCT (n=412)
Open-label
2 × 3 factorial design
Yes
Does the choice of insulin analogue regimen (biphasic, basal-bolus, or basal) reduce carotid intima-media thickness in patients with type 2 diabetes?
Absolute Event Rate: -0.009% vs -0.012%
Different insulin analogue regimens did not significantly differ in their effect on carotid intima-media thickness progression over 18 months in patients with type 2 diabetes, though the trial was underpowered.
No carotid IMT difference among insulin regimens in type 2 diabetes; confirms equivalent effects on subclinical atherosclerosis.
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.
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Lundby‐Christensen et al. (2016) conducted an RCT in type 2 diabetes mellitus (n=412). Biphasic insulin aspart or insulin aspart plus insulin detemir vs. Insulin detemir alone once daily was evaluated on change in mean carotid IMT. Carotid IMT change did not differ between 18 months of treatment with biphasic insulin aspart (-0.009 mm), aspart plus detemir (0.000 mm), or detemir alone (-0.012 mm) in type 2 diabetes.
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