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Diabetes Technol Ther. 2012 Jun;14(6):508-14. doi: 10.1089/dia.2011.0208. Epub 2012 Feb 29.

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.

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Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.



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.


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.


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%.


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.

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