title: Insulin lispro low mixture twice daily versus basal insulin glargine once daily and prandial insulin lispro once daily in patients with type 2 diabetes requiring insulin intensification: a randomized phase IV trial.
abstract: OBJECTIVE
  To compare the efficacy and safety of two insulin intensification strategies in patients with type 2 diabetes inadequately controlled on basal insulin glargine with metformin and/or pioglitazone.
  
  
  METHODS
  A multinational, randomized, open-label trial that compared insulin lispro low mixture (LM25; n = 236) twice daily with a basal-prandial regimen of insulin glargine once daily and insulin lispro once daily (IGL; n = 240) over 24 weeks in patients with HbA1c 7.5-10.5% and fasting plasma glucose ≤ 6.7 mmol/l. The primary objective was to assess non-inferiority [per-protocol (PP) population], and then superiority [intention-to-treat (ITT) population], of LM25 versus IGL according to change in HbA1c after 24 weeks (non-inferiority margin 0.4%, two-sided significance level 0.05).
  
  
  RESULTS
  Estimated change [least squares (LS) mean (95% CI)] in HbA1c after 24 weeks: -1.30 (-1.44, -1.16)% with LM25 and -1.08 (-1.22, -0.94)% with IGL. Non-inferiority was shown [LS mean (95% CI) HbA1c treatment difference -0.21 (-0.38, -0.04) (PP population)]; gated superiority assessment showed a statistically significant advantage for LM25 (p = 0.010; ITT population). Mean blood glucose, glycaemic variability, overall tolerability and hypoglycaemic episodes per patient-year did not show significant differences between treatments during the study.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes inadequately controlled on once-daily basal insulin glargine and metformin and/or pioglitazone, intensification with LM25 was superior to a basal-prandial approach in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycaemia episodes.
authors.affiliation: Hospital Universitario Virgen de la Victoria, Málaga and CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Malaga, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Tinahones
authors.forename: J L
authors.initials: JL
authors.lastname: Gross
authors.forename: A
authors.initials: A
authors.lastname: Onaca
authors.forename: S
authors.initials: S
authors.lastname: Cleall
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D062407:Meals; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D008687:Metformin; D000077205:Pioglitazone; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human
keywords: insulin glargine; insulin intensification; insulin lispro; insulin lispro mixture; type 2 diabetes
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