title: TREATMENT INTENSIFICATION WITH INSULIN DEGLUDEC/INSULIN ASPART TWICE DAILY: RANDOMIZED STUDY TO COMPARE SIMPLE AND STEP-WISE TITRATION ALGORITHMS.
abstract: OBJECTIVE
  This 26-week, multicenter, randomized, open-label, parallel-group, treat-to-target trial in adults with type 2 diabetes compared the efficacy and safety of treatment intensification algorithms with twice-daily (BID) insulin degludec/insulin aspart (IDegAsp).
  
  
  METHODS
  Patients randomized 1:1 to IDegAsp BID used either a 'Simple' algorithm (twice-weekly dose adjustments based on a single prebreakfast and pre-evening meal self-monitored plasma glucose [SMPG] measurement; IDegAsp[BIDSimple], n = 136) or a 'Stepwise' algorithm (once-weekly dose adjustments based on the lowest of 3 pre-breakfast and 3 pre-evening meal SMPG values; IDegAsp[BIDStep-wise], n = 136).
  
  
  RESULTS
  After 26 weeks, mean change from baseline in glycated hemoglobin (HbA1c) with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise] (-15 mmol/mol versus -14 mmol/mol; 95% confidence interval [CI] upper limit, <4 mmol/mol) (baseline HbA1c: 66.3 mmol/mol IDegAsp[BIDSimple] and 66.6 mmol/mol IDegAsp[BIDStep-wise]). The proportion of patients who achieved HbA1c <7.0% (<53 mmol/mol) at the end of the trial was 66.9% with IDegAsp[BIDSimple] and 62.5% with IDegAsp[BIDStep-wise]. Fasting plasma glucose levels were reduced with each titration algorithm (-1.51 mmol/L IDegAsp[BIDSimple] versus -1.95 mmol/L IDegAsp[BIDStep-wise]). Weight gain was 3.8 kg IDegAsp[BIDSimple] versus 2.6 kg IDegAsp[BIDStep-wise], and rates of overall confirmed hypoglycemia (5.16 episodes per patient-year of exposure [PYE] versus 8.93 PYE) and nocturnal confirmed hypoglycemia (0.78 PYE versus 1.33 PYE) were significantly lower with IDegAsp[BIDStep-wise] versus IDegAsp[BIDSimple]. There were no significant differences in insulin dose increments between groups.
  
  
  CONCLUSIONS
  Treatment intensification with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise]. Both titration algorithms were well tolerated; however, the more conservative step-wise algorithm led to less weight gain and fewer hypoglycemic episodes. Clinicaltrials.gov: NCT01680341.
authors.forename: Gregg
authors.initials: G
authors.lastname: Gerety
authors.forename: Wan Mohamad Wan
authors.initials: WM
authors.lastname: Bebakar
authors.forename: Louis
authors.initials: L
authors.lastname: Chaykin
authors.forename: Mesut
authors.initials: M
authors.lastname: Ozkaya
authors.forename: Stanislava
authors.initials: S
authors.lastname: Macura
authors.forename: Malene Lundgren
authors.initials: ML
authors.lastname: Hersløv
authors.forename: Thomas
authors.initials: T
authors.lastname: Behnke
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C578220:insulin degludec, insulin aspart drug combination