Abstract
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 (HbA1c) 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 HbA1c 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 HbA1c 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).