title: Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial.
abstract: BACKGROUND
  Intensive basal-bolus insulin therapy has been shown to improve glycaemic control and reduce the risk of long-term complications that are associated with type 1 diabetes mellitus. Insulin degludec is a new, ultra-longacting basal insulin. We therefore compared the efficacy and safety of insulin degludec and insulin glargine, both administered once daily with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes.
  
  
  METHODS
  In an open-label, treat-to-target, non-inferiority trial, undertaken at 79 sites (hospitals and centres) in six countries, adults (aged ≥18 years) with type 1 diabetes (glycated haemoglobin [HbA(1c)] ≤10% [86 mmol/mol]), who had been treated with basal-bolus insulin for at least 1 year, were randomly assigned in a 3:1 ratio, with a computer-generated blocked allocation sequence, to insulin degludec or insulin glargine without stratification by use of a central interactive response system. The primary outcome was non-inferiority of degludec to glargine, assessed as a reduction in HbA(1c) after 52 weeks, with the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00982228.
  
  
  RESULTS
  Of 629 participants, 472 were randomly assigned to insulin degludec and 157 to insulin glargine; all were analysed in their respective treatment groups. At 1 year, HbA(1c) had fallen by 0·40% points (SE 0·03) and 0·39% points (0·07), respectively, with insulin degludec and insulin glargine (estimated treatment difference -0·01% points [95% CI -0·14 to 0·11]; p<0·0001 for non-inferiority testing) and 188 (40%) and 67 (43%) participants achieved a target HbA(1c) of less than 7% (<53 mmol/mol). Rates of overall confirmed hypoglycaemia (plasma glucose <3·1 mmol/L or severe) were similar in the insulin degludec and insulin glargine groups (42·54 vs 40·18 episodes per patient-year of exposure; estimated rate ratio [degludec to glargine] 1·07 [0·89 to 1·28]; p=0·48). The rate of nocturnal confirmed hypoglycaemia was 25% lower with degludec than with glargine (4·41 vs 5·86 episodes per patient-year of exposure; 0·75 [0·59 to 0·96]; p=0·021). Overall serious adverse event rates (14 vs 16 events per 100 patient-years of exposure) were similar for the insulin degludec and insulin glargine groups.
  
  
  CONCLUSIONS
  Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycaemic control while lowering the risk of nocturnal hypoglycaemia, which is a major limitation of insulin therapy.
  
  
  BACKGROUND
  Novo Nordisk.
authors.affiliation: University of Sheffield, Sheffield, UK. s.heller@sheffi eld.ac.uk
authors.forename: Simon
authors.initials: S
authors.lastname: Heller
authors.forename: John
authors.initials: J
authors.lastname: Buse
authors.forename: Miles
authors.initials: M
authors.lastname: Fisher
authors.forename: Satish
authors.initials: S
authors.lastname: Garg
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Ludwig
authors.initials: L
authors.lastname: Merker
authors.forename: Eric
authors.initials: E
authors.lastname: Renard
authors.forename: David
authors.initials: D
authors.lastname: Russell-Jones
authors.forename: Areti
authors.initials: A
authors.lastname: Philotheou
authors.forename: Ann Marie Ocampo
authors.initials: AM
authors.lastname: Francisco
authors.forename: Huiling
authors.initials: H
authors.lastname: Pei
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D061267:Insulin Aspart / Q000008:administration & dosage*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; C571886:insulin degludec