title: Initiation and gradual intensification of premixed insulin lispro therapy versus Basal {+/-} mealtime insulin in patients with type 2 diabetes eating light breakfasts.
abstract: OBJECTIVE
  We compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal ± mealtime insulin analog in patients eating light breakfasts.
  
  
  METHODS
  This 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 HbA1c after 48 weeks, assessed using ANCOVA with a 0.4% margin.
  
  
  RESULTS
  Patients (n = 344; 176 [51%] females; mean [SD] age 54.3 [8.8] years; BMI 29.4 [4.6] kg/m(2); baseline HbA1c 9.02 [0.97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA1c were 7.40% (7.15-7.65) and 7.55% (7.27-7.82) in respective arms. Between-treatment difference was -0.14% (-0.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA1c 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.
  
  
  CONCLUSIONS
  Both intensive insulin strategies improved glycemic control; however, final HbA1c 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 HbA1c <7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal-bolus regimen.
authors.affiliation: Corresponding author: Dario Giugliano, dario.giugliano@unina2.it.
authors.forename: Dario
authors.initials: D
authors.lastname: Giugliano
authors.forename: Mariusz
authors.initials: M
authors.lastname: Tracz
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Shah
authors.forename: Alfonso
authors.initials: A
authors.lastname: Calle-Pascual
authors.forename: Cristina
authors.initials: C
authors.lastname: Mistodie
authors.forename: Rui
authors.initials: R
authors.lastname: Duarte
authors.forename: Ramazan
authors.initials: R
authors.lastname: Sari
authors.forename: Vincent
authors.initials: V
authors.lastname: Woo
authors.forename: Alina O
authors.initials: AO
authors.lastname: Jiletcovici
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deinhard
authors.forename: Simone A
authors.initials: SA
authors.lastname: Wille
authors.forename: Jacek
authors.initials: J
authors.lastname: Kiljanski
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D062408:Breakfast; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007267:Injections; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting