28‐week, randomized, multicenter, open‐label, parallel‐group phase III trial to investigate the efficacy and safety of biphasic insulin aspart 70 thrice‐daily injections vs twice‐daily injections of biphasic insulin aspart 30 in patients with type 2 diabetes

Aims/Introduction: An insulin analogue formulation with a 7:3 ratio of rapid‐acting and intermediate‐acting fractions, biphasic insulin aspart 70 (BIAsp70) was developed to supplement basal insulin between meals and mimic the physiological pattern of postprandial insulin secretion. Materials and Methods: We carried out a randomized, open‐label study to compare the efficacy and safety profiles of BIAsp70 and an insulin analogue formulation with a 3:7 ratio of rapid‐acting and intermediate‐acting fractions (BIAsp30) in type 2 diabetes mellitus patients. Patients were randomized and received either thrice‐daily BIAsp70 (n = 145) or twice‐daily BIAsp30 (n = 144) for 28 weeks. The primary end‐point was glycated hemoglobin (HbA(1c)) after 16 weeks of treatment. Results: Non‐inferiority of BIAsp70 vs BIAsp30 was confirmed and superiority was established with a between‐group difference (BIAsp70–BIAsp30) in HbA(1c) after 16 weeks of treatment of −0.35% (95% CI: −0.51 to −0.19; P < 0.0001 for superiority). The mean postprandial glucose increment (19.96 vs 54.35 mg/dL; P < 0.0001) and M‐value (12.99 vs 17.94; P < 0.0001) at 16 weeks were smaller in the BIAsp70 group than in the BIAsp30 group, and were maintained at 28 weeks. Pre‐breakfast glucose (157.9 vs 140.7 mg/dL), total insulin dose (46.8 vs 38.1 U/day) and weight gain (+1.94 vs 1.23 kg) at week 28 were greater in the BIAsp70 group. Incidence of nocturnal hypoglycemia was significantly lower with BIAsp70 vs BIAsp30 (1.23 vs 3.21 events/subject year; P = 0.0002) at week 28. Conclusions: Thrice‐daily BIAsp70 was superior to twice‐daily BIAsp30 in terms of HbA(1c) change, with less variation in daytime plasma glucose profiles. BIAsp70 was well tolerated, with a lower incidence of nocturnal hypoglycemia vs BIAsp30. This trial was registered with ClinicalTrial.gov (no. NCT00318786). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00015.x, 2010)