Prandial-basal insulin regimens plus oral antihyperglycaemic agents to improve mealtime glycaemia: initiate and progressively advance insulin therapy in type 2 diabetes

• Published in: Diabetes, obesity & metabolism Vol. 12; no. 11; pp. 967 - 975
• Main Authors: Jain, S.M, Mao, X, Escalante-Pulido, M, Vorokhobina, N, Lopez, I, Ilag, L.L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.11.2010; Blackwell Publishing Ltd; Wiley Subscription Services, Inc
• Subjects: basal and bolus therapy; Blood glucose; Blood Glucose - metabolism; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Female; Glycated Hemoglobin A - metabolism; Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Insulin; Insulin - pharmacology; Insulin - therapeutic use; insulin glargine; insulin lispro; Male; Middle Aged; Original; Postprandial Period; prandial premixed therapy; Treatment Outcome; type 2 diabetes mellitus
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2010.01287.x

Aims: To compare two progressive approaches [once-daily insulin glargine plus [less-than or equal to]3 mealtime lispro (G+L) vs. insulin lispro mix 50/50 (LM50/50) progression once up to thrice daily (premix progression, PP)] of beginning and advancing insulin in patients with type 2 diabetes (T2D) and inadequate glycaemic control on oral therapy, with the aim of showing non-inferiority of PP to G+L. Methods: Patients were randomized to PP (n = 242) or G+L (n = 242) in a 36-week, multinational, open-label trial. Dinnertime insulin LM 50/50 could be replaced with insulin lispro mix 75/25 if needed for fasting glycaemic control. Results: Baseline haemoglobin A1c (HbA1c) were 9.5% (PP) and 9.3% (G+L); p = 0.095. Change in A1C (baseline to endpoint) was -1.76% (PP) and -1.93% (G+L) (p = 0.097) [between-group difference of 0.17 (95% confidence interval: -0.03, 0.37)]. Non-inferiority of PP to G+L was not shown based on the prespecified non-inferiority margin of 0.3%. A1C was lower with G+L at weeks 12 (7.8 vs. 7.9%; p = 0.042), 24 (7.4 vs. 7.6%; p = 0.046), but not at week 36 (7.5 vs. 7.6%; p = 0.405). There were no significant differences in percentages of patients achieving A1C [less-than or equal to]7%, overall hypoglycaemia incidence and rate or weight change. Total daily insulin dosages at endpoint were higher with PP vs. G+L (0.57 vs. 0.51 U/kg; p = 0.017), likely due to more injections (1.98 vs. 1.79; p = 0.011). Conclusions: Both treatments progressively improved glycaemic control in patients with T2D on oral therapy, although non-inferiority of PP to G+L was not shown. Higher insulin doses were observed with PP with no between-treatment differences in overall hypoglycaemia or weight gain.