Improved glycaemic control of thrice-daily biphasic insulin aspart compared with twice-daily biphasic human insulin; a randomized, open-label trial in patients with type 1 or type 2 diabetes

Aim: This trial evaluated the potential for improving glycaemic control by intensifying a conventional twice‐daily therapy with premixed human insulin (HI) to a thrice‐daily regimen using premixed formulations of biphasic insulin aspart (BIAsp) in patients with type 1 or type 2 diabetes. Methods: This was a multicentre, open‐label, parallel group trial. After a 4‐week run‐in period, patients were randomized 1 : 1 to 16 weeks of treatment. A total of 748 patients were screened, 664 were exposed to trial drug and 604 completed the trial. Results: Haemoglobin A1c, the primary efficacy endpoint, was shown to be significantly lower for the BIAsp treatment group compared with the biphasic HI (BHI) 30 group [estimated mean difference: −0.32, 95% confidence interval (CI) (−0.48; −0.16), p = 0.0001]. The average blood glucose level was significantly lower in the BIAsp group [estimated mean difference: −0.79, 95% CI (−1.17; −0.40), p = 0.0001]. There were few major hypoglycaemic episodes, 11 in the BIAsp group and 7 in the BHI 30 group. Although intensification of insulin therapy with BIAsp three times a day was associated with a higher risk of minor hypoglycaemia (relative risk = 1.58, p = 0.0038), the overall rate of minor hypoglycaemia remained low with both the BIAsp and the BHI treatments (13.1 vs. 8.3 episodes/patient year respectively). Overall safety and patient satisfaction were similar with the two insulin therapies. Conclusions: This trial confirmed that a thrice‐daily BIAsp regimen can safely be used to intensify treatment for patients inadequately controlled on twice‐daily BHI. A treat‐to‐target trial is required to explore the full potential of the BIAsp regimens and evaluate their use as a viable alternative to intensification with a basal‐bolus regimen.