title: Insulin glargine compared with premixed insulin for management of insulin-naïve type 2 diabetes patients uncontrolled on oral antidiabetic drugs: the open-label, randomized GALAPAGOS study.
abstract: OBJECTIVE
  Demonstrate superiority of insulin glargine (±glulisine) strategy versus premixed insulin strategy for percentage of patients reaching HbA1c <7% (<53 mmol/mol) at study end without any documented symptomatic hypoglycemia (bloof glucose [BG] ≤3.1 mmol/L) in type 2 diabetes (T2DM) patients failing oral agents.
  
  
  METHODS
  This 24-week, open-label, multinational trial randomized patients to glargine OD or premix OD or BID, continuing metformin ± insulin secretagogue (IS). Second premix injection could be added any time; glulisine could be added with main meal in glargine OD patients with HbA1c ≥7% and fasting blood glucose (FBG) <7 mmol/L at week 12. IS was stopped with any second injection. Insulin titration targeted FBG ≤5.6 mmol/L.
  
  
  RESULTS
  Modified intent-to-treat population comprised 923 patients (glargine, 462; premix, 461). Baseline characteristics were similar (mean T2DM duration: 9 years; HbA1c: 8.7% (72 mmol/mol); FBG: 10.4 mmol/L). Primary endpoint was achieved by 33.2% of glargine (±glulisine) and 31.4% of premix patients. Superiority was not demonstrated, but non-inferiority was (pre-specified margin: 25% of premix rate). More patients using premix achieved target (52.6% vs. 43.2%, p=0.005); symptomatic hypoglycemia was less with glargine (1.17 vs. 2.93 events/patient-year).
  
  
  CONCLUSIONS
  Glargine (±glulisine) and premix strategies resulted in similar percentages of well-controlled patients without hypoglycemia, with more patients achieving target HbA1c with premix whereas overall symptomatic hypoglycemia was less with glargine.
authors.affiliation: Pontificia Universidad Javeriana, Hospital Universitario San Ignacio, Bogotá, Colombia. Electronic address: paschner@cable.net.co.
authors.forename: Pablo
authors.initials: P
authors.lastname: Aschner
authors.affiliation: CARE Hospital, Hyderabad, India. Electronic address: sethibipin54@gmail.com.
authors.forename: Bipin
authors.initials: B
authors.lastname: Sethi
authors.affiliation: Unit of Endocrinology and Nutrition, Hospital General de Segovia, Segovia, Spain. Electronic address: fgomezperalta@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez-Peralta
authors.affiliation: Sanofi, Frankfurt, Germany. Electronic address: wolfgang.landgraf@sanofi.com.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Landgraf
authors.affiliation: Lincoln, Boulogne-Billancourt, France. Electronic address: Virginie.Loizeau-prest@sanofi.com.
authors.forename: Virginie
authors.initials: V
authors.lastname: Loizeau
authors.affiliation: Sanofi, Paris, France. Electronic address: dainmariepaule@yahoo.fr.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Dain
authors.affiliation: Sanofi, Paris, France. Electronic address: Valerie.pilorget@sanofi.com.
authors.forename: Valerie
authors.initials: V
authors.lastname: Pilorget
authors.affiliation: Division of Endocrinology and Metabolism, School of Medicine, Dokuz Eylul University, Izmir, Turkey. Electronic address: drcomlekci@hotmail.com.
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Comlekci
mesh_terms: D000284:Administration, Oral; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007267:Injections; D007328:Insulin / Q000008:administration & dosage*; D000069036:Insulin Glargine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine
keywords: GALAPAGOS; Hypoglycemia; Insulin glargine; Premixed insulin; Type 2 diabetes