title: Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: Flex T1): a 26-week randomized, treat-to-target trial with a 26-week extension.
abstract: OBJECTIVE
  This study investigated the efficacy and safety of insulin degludec (IDeg) once daily (OD), varying injection timing day to day in subjects with type 1 diabetes.
  
  
  METHODS
  This 26-week, open-label, treat-to-target, noninferiority trial compared IDeg forced flexible (Forced-Flex) OD (given in a fixed schedule with a minimum 8 and maximum 40 hours between doses) with IDeg or insulin glargine (IGlar) given at the same time daily OD. In the 26-week extension, all IDeg subjects were transferred to a free-flexible (Free-Flex) regimen, which allowed any-time-of-day dosing, and compared with subjects continued on IGlar.
  
  
  RESULTS
  After 26 treatment weeks, mean glycosylated hemoglobin was reduced with IDeg Forced- Flex (-0.40%), IDeg (-0.41%), and IGlar (-0.58%). IDeg Forced-Flex noninferiority was achieved. Fasting plasma glucose reductions were similar with IDeg Forced-Flex and IGlar but greater with IDeg (-2.54 mmol/L) than IDeg Forced-Flex (-1.28 mmol/L) (P = .021). At week 52, IDeg Free-Flex subjects had similar glycosylated hemoglobin but greater fasting plasma glucose reductions than IGlar subjects (-1.07 mmol/L) (P = .005). Confirmed hypoglycemia rates (plasma glucose <3.1 mmol/L or severe hypoglycemia) were similar at weeks 26 and 52. Nocturnal confirmed hypoglycemia was lower with IDeg Forced-Flex vs IDeg (37%; P = .003) and IGlar (40%; P = .001) at week 26 and 25% lower with IDeg Free-Flex vs IGlar (P = .026) at week 52.
  
  
  CONCLUSIONS
  IDeg can be administered OD at any time of day, with injection timing varied without compromising glycemic control or safety vs same-time-daily IDeg or IGlar. This may improve basal insulin adherence by allowing injection-time adjustment according to individual needs.
authors: Clinical and Experimental Endocrinology, UZ Herestraat 49, Box 902, Room 08.43, 3000 Leuven, Belgium. chantal.mathieu@uzleuven.be
authors: Chantal
authors: C
authors: Mathieu
authors: Priscilla
authors: P
authors: Hollander
authors: Bresta
authors: B
authors: Miranda-Palma
authors: John
authors: J
authors: Cooper
authors: Edward
authors: E
authors: Franek
authors: David
authors: D
authors: Russell-Jones
authors: Jens
authors: J
authors: Larsen
authors: Søren Can
authors: SC
authors: Tamer
authors: Stephen C
authors: SC
authors: Bain
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012646:Self Administration; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C571886:insulin degludec
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