title: Efficacy and safety of a premixed versus a basal-plus insulin regimen as intensification for type 2 diabetes by timing of the main meal.
abstract: To describe the efficacy and safety of premixed insulin lispro protamine suspension 75%/insulin lispro solution 25% (LM25) twice daily (bid) versus basal insulin glargine plus prandial insulin lispro (IGL), both once daily, according to main meal timing.
  
  
  
  Data were obtained post hoc from a 24 week, randomized, open-label study comparing LM25 and IGL as insulin intensification in patients with type 2 diabetes inadequately controlled with once daily basal insulin glargine plus metformin and/or pioglitazone (ClinicalTrials.gov identifier: NCT01175824). Patients administered LM25 bid before breakfast and the evening meal, insulin glargine at bedtime and insulin lispro before the day's main meal (meal with the highest 2 hour postprandial glucose level during screening). Patients were grouped by main meal. Changes in glycosylated hemoglobin (HbA1c) and bodyweight were summarized using likelihood-based mixed models; hypoglycemia incidence was compared between treatments using Fisher's exact test.
  
  
  
  Overall, 476 patients (LM25, n = 236; IGL, n = 240) were randomized. In all main meal groups, with both insulin regimens, mean HbA1c significantly decreased from baseline to 24 weeks (p < 0.0001). Patients whose main meal was in the evening had a greater bodyweight increase with LM25 than with IGL (p = 0.015), and a smaller proportion of these patients experienced total (p = 0.027) and nocturnal (p = 0.006) hypoglycemia with LM25 compared with IGL. Patients whose main meal was lunch experienced more nocturnal hypoglycemia with LM25 than with IGL (p = 0.030). Study limitations include that this was a post hoc analysis and no assessments ensured that: SMBG results determined timing of the main meal, each patient's main meal remained unchanged throughout the study, or patients administered insulin lispro with that meal.
  
  
  
  Glycemic control improved in patients receiving either LM25 or IGL, irrespective of main meal timing. Both regimens can be used in patients with inadequate glycemic control who are in need of insulin intensification.
authors.affiliation: a Centro de Pesquisas em Diabetes , Porto Alegre , Rio Grande do Sul , Brazil ;
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gross
authors.affiliation: b Centro de Diabetes de Coatzacoalcos , Veracruz , México ;
authors.forename: Arturo
authors.initials: A
authors.lastname: Rojas
authors.affiliation: c Diabetes Action Centre , Mumbai , India ;
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Shah
authors.affiliation: d Hospital Universitario Virgen de la Victoria , Málaga , Spain ;|e IBIMA, CIBER Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III , Málaga , Spain ;
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: f Eli Lilly and Company , Windlesham , United Kingdom ;
authors.forename: Simon
authors.initials: S
authors.lastname: Cleall
authors.affiliation: g Lilly Spain , Alcobendas , Madrid , Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Rodríguez
mesh_terms: D000368:Aged; D001786:Blood Glucose; D002985:Clinical Protocols; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D000069036:Insulin Glargine / Q000627:therapeutic use*; D061268:Insulin Lispro / Q000627:therapeutic use*; D016013:Likelihood Functions; D008297:Male; D062407:Meals; D008875:Middle Aged; D019518:Postprandial Period; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D061268:Insulin Lispro
keywords: Insulin glargine; Insulin intensification; Insulin lispro mixture; main meal; prandial insulin lispro; type 2 diabetes