title: Efficacy and Safety of Flexible Versus Fixed Dosing Intervals of Insulin Glargine 300 U/mL in People with Type 2 Diabetes.
abstract: BACKGROUND
  Insulin glargine 300 U/mL (Gla-300) has a more constant and prolonged action profile than insulin glargine 100 U/mL and in clinical studies is associated with similar glycemic control but less hypoglycemia. Whether its effects are altered by variability of injection time was examined in two 3-month substudies.
  
  
  METHODS
  Eligible participants completing 6 months of optimized treatment with Gla-300 in EDITION 1 (n = 109) and EDITION 2 (n = 89), having a mean hemoglobin A1c (HbA1c) level of 7.3 % (SD 1.0 %), were randomized (1:1) to groups advised to increase variability of between-injection intervals to 24 ± up to 3 h or to maintain fixed 24-h intervals for 3 months. Changes of HbA1c level and other efficacy and safety measures were assessed.
  
  
  RESULTS
  In the fixed-dosing group, 64% of participants reported all intervals within the 23-25-h range, compared with 15% of those advised flexible dosing. In the fixed- and flexible-dosing groups, 12% and 41%, respectively, of between-injection intervals were outside the 23-25-h range, and 2% and 16%, respectively, were outside the 21-27-h range. Least squares mean between-group difference in HbA1c change from baseline was 0.05 % (95% confidence interval [CI], -0.13 to 0.23); for fasting plasma glucose, 2.7 mg/dL (95% CI, -9.0 to 14.4); and for daily basal insulin dose, 0.00 U/kg (95% CI, -0.02 to 0.03). Frequencies of hypoglycemia and adverse events did not differ between groups.
  
  
  CONCLUSIONS
  The efficacy and safety of Gla-300 demonstrated in EDITION 1 and EDITION 2 are maintained in substudies when the insulin was injected up to 3 h before or after the usual time of administration.
authors: 1 Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University , Portland, Oregon.
authors: Matthew C
authors: MC
authors: Riddle
authors: 2 University of Perugia , Perugia, Italy .
authors: Geremia B
authors: GB
authors: Bolli
authors: 3 Newcastle University , Newcastle upon Tyne, United Kingdom .
authors: Philip D
authors: PD
authors: Home
authors: 4 International Diabetes Center at Park Nicollet , Minneapolis, Minnesota.
authors: Richard M
authors: RM
authors: Bergenstal
authors: 5 Sanofi-Aventis Deutschland GmbH , Frankfurt am Main, Germany .
authors: Monika
authors: M
authors: Ziemen
authors: 5 Sanofi-Aventis Deutschland GmbH , Frankfurt am Main, Germany .
authors: Isabel
authors: I
authors: Muehlen-Bartmer
authors: 6 Sanofi , Warsaw, Poland .
authors: Marek
authors: M
authors: Wardecki
authors: 7 EXPERIS IT , Nanterre, France .
authors: Laetitia
authors: L
authors: Vinet
authors: 8 CHRU Strasbourg, University of Strasbourg , France .
authors: Nathalie
authors: N
authors: Jeandidier
authors: 9 University of Helsinki , Helsinki, Finland .
authors: Hannele
authors: H
authors: Yki-Järvinen
mesh_terms: D000203:Activities of Daily Living; D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D008297:Male; D062407:Meals; D055118:Medication Adherence
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; C517652:hemoglobin A1c protein, human