OBJECTIVE - The rapid-acting insulin analogs aspart, and lispro have now been developed in biphasic formulations. This trial compared the postprandial serum glucose control of biphasic insulin aspart 30 (BIAsp 30 : 30% aspart, 70% protaminated aspart) with that of biphasic insulin lispro 25 (Mix25 : 25% lispro, 75% protaminated lispro) and biphasic human insulin 30 (BHI 30 : 30% regular insulin, 70% NPH insulin) in insulm-treated subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS - This was an open-labeled, randomized, single-dose, three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who had no significant late diabetic complications. BIAsp 30 and Mix25 were injected subcutaneously immediately before a test meal, and BHI 30 was injected 15 min before a test meal. The primary target of analysis was serum glucose excursion 0-5 h after a meal. RESULTS - The postprandial glycemic control with BIAsp 30, as assessed by the 5-h post-meal serum glucose excursion, was superior to that with both BHI 30 and Mix25 (16.6 +/- 4.5 vs. 20.1 +/- 4.9 and 18.9 +/- 6.1 mmol/l per hour, respectively; P < 0.001. and P < 0.05). For BIAsp 30 versus BHI 30, this was supported by a reduced maximum glucose concentration [C-max(SG)] (- 5%; P < 0.05) occurring earlier (- 13 min; P < 0.01.). Furthermore, BIAsp 30 displayed a higher maximum serum insulin concentration (+ 101% P < 0.001) occurring earlier (- 55 min. P < 0.001) compared with BHI 30. Compared with Mix25, there was a shorter time to C-max(SG) (- 11 min, P < 0.05) after treatment With BIAsp 30. CONCLUSIONS - This trial demonstrates that BIAsp 30 improves postprandial glycemic control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes.