Background Lispro Mix 25% insulin lispro/75% insulin lispro protamine (LM25) and Lispro Mix 50% insulin lispro/50% insulin lispro protamine (LM50) were compared as starter insulins in East Asian patients with type 2 diabetes. Methods Phase 4, open-label, randomized trial conducted in China, Japan, Korea, and Turkey. Subjects received twice-daily LM25 (n=207) or LM50 (n=196) for 26 weeks. The primary outcome was the HbA(1c) change from baseline. Results The least squares mean changes from baseline in HbA(1c) are -1.52% and -1.69% for LM25 and LM50, respectively, and the least squares mean difference [95% CI] is 0.17% [-0.01, 0.35]. More subjects in the LM50 group than in the LM25 group achieved HbA(1c) targets of <7.0% (59.7% versus 45.9%, respectively; p=0.007). LM50 was more effective than LM25 in reducing postprandial glucose after the morning (mean difference in change from baseline, 0.56 mmol/L; p=0.038) and evening (1.11 mmol/L; p<0.001) meals. The reduction in fasting blood glucose was significantly greater (p=0.046) in the LM25 group (LS mean [95% CI] change from baseline: -2.37 mmol/L [-2.68, -2.06]) than in the LM50 group (-1.99 mmol/L [-2.30, -1.68]). LM50 was more effective than LM25 in reducing HbA(1c) in subjects with baseline HbA(1c), postprandial glucose, or carbohydrate intake levels greater than the median levels. Hypoglycemia rates and weight gain were similar between groups. Conclusions LM25 and LM50 were noninferior to each other in improving glycemic control in Asian patients with type 2 diabetes. In addition, LM50 was more efficacious than LM25 with respect to the percentage of subjects reaching target HbA(1c) levels. Copyright (C) 2016 John Wiley & Sons, Ltd.