OBJECTIVEWe compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal 6 mealtime insulin analog in patients eating light breakfasts. RESEARCH DESIGN AND METHODSThis randomized, open-label, 48-week study compared two algorithms. Up to three injections of insulin lispro mix 25 and/or insulin lispro mix 50 (premix; premixed insulin lispro) or basal insulin glargine plus up to three injections of insulin lispro (basal+; glargine + insulin lispro) were used in type 2 diabetic patients uncontrolled with oral antihyperglycemic medication and consuming <15% daily calories at breakfast. The hypothesis was to test noninferiority of premix to basal+ for glycemic control measured by HbA 1c after 48 weeks, assessed using ANCOVA with a 0.4% margin. 97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA 1c were 7.40% (7.15-7.65) and 7.55% (7.27-7.82) in respective arms. Between-treatment difference was 20.14% (20.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA 1c targets of <7.0% compared with basal+ (48.2 vs. 36.2%; P = 0.024). Self-monitored blood glucose profiles, body weight changes, total insulin doses, and overall hypoglycemia (65 vs. 60%) were similar in premix and basal+ (P = 0.494), except nocturnal episodes (34.3 vs. 23.7%; P = 0.018) were more common in premix. RESULTS Patients CONCLUSIONSBoth intensive insulin strategies improved glycemic control; however, final HbA 1c levels were seen above those achieved in previous treat-to-target trials, likely due to the inadequate insulin titrations and probably due to the complexity of tested insulin regimens. A higher percentage of patients achieved target HbA 1c <7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal-bolus regimen.

In this patient sample, usage of a memory function pen was not associated with superior glycemic control, suggesting that adherence to mealtime injection schedules was not improved in a relevant manner. The memory function might be helpful for specific patient populations only, e.g., children or forgetful patients.