Higher morning to evening ratio in total dose of twice-daily biphasic insulin analog might be effective in achieving glucose control in patients with poorly controlled type 2 diabetes

Background: The aims of this study are to investigate not only the glucose-lowering effectiveness of twice-daily premixed insulin lispro 25 (Humalog® Mix25™, Eli Lilly and Co., Indianapolis, IN), but also the optimal divided ratio of total Mix25 dose in Korean patients with poorly controlled type 2 diabetes. Subjects and Methods: In this retrospective study, we retrieved data for subjects who were on intensive insulin therapy with twice-daily Mix25 regimen for at least 24 weeks. Changes of hemoglobin A1c (HbA _1c) and other clinical and laboratory parameters were evaluated. Two groups were defined according to dose ratio of pre-breakfast to pre-dinner insulin at 24 weeks: Group I, pre-breakfast:pre-dinner insulin dose ratio=50:50; Group II, ratio=53:47-75:25. Results: In total, 143 subjects were ultimately analyzed in this study. Twice-daily Mix25 significantly improved HbA _1c levels from 10.1% to 7.7%, and 34% of patients had reached the target glycemic goal (HbA _1c<7%) after 24 weeks. Compared with Group I, a significant reduction in HbA _1c (Group I vs. Group II, -1.9±0.3% vs. -2.8±0.3%, P=0.02) and a larger proportion of subjects with HbA _1c<7% (23.2% vs. 46.7%, P=0.01) were observed in subjects in Group II. Among clinical and laboratory factors, duration of diabetes (odd ratios [OR]=0.93, 95% confidence interval [CI] 0.86-0.99, P=0.04) and history of sulfonylurea use (OR=0.27, 95% CI 0.10-0.72, P=0.01) were independently associated with achieving target HbA _1c levels less than 7%. Conclusions: Twice-daily Mix25 is an effective option for Korean subjects with type 2 diabetes having uncontrolled hyperglycemia. A higher pre-breakfast/pre-dinner dose ratio (53:47-75:25) might be taken into consideration as an initial protocol to accomplish better glycemic control in twice-daily Mix25.