title: Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial.
abstract: To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naïve patients with type 2 diabetes.
  
  
  
  This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n = 210).
  
  
  
  Mean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once-weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [-0.04; 0.28]95%CI, 1.30 mmol/mol [-0.41; 3.01]95%CI). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was -1.0 kg vs -2.0 kg for once-weekly vs twice-weekly titration. Rates of severe or blood glucose-confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient-year of exposure (PYE) for once-weekly, 0.76 events/PYE for twice-weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once-weekly and twice-weekly titration, respectively.
  
  
  
  A pragmatic titration algorithm with once-weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice-weekly adjustments based on 3 preceding PG values in insulin-naïve patients.
authors.affiliation: Schulich School of Medicine & Dentistry, London, Ontario, Canada.
authors.forename: Stewart B
authors.identifier: 0000-0002-1794-6551
authors.initials: SB
authors.lastname: Harris
authors.affiliation: Péterfy Hospital and Emergency Center, Budapest, Hungary.
authors.forename: Győző
authors.initials: G
authors.lastname: Kocsis
authors.affiliation: Hietzing Hospital, Vienna, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Prager
authors.affiliation: American Health Network, Indianapolis, Indiana.
authors.forename: Terry
authors.initials: T
authors.lastname: Ridge
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Keval
authors.initials: K
authors.lastname: Chandarana
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Natalie
authors.initials: N
authors.lastname: Halladin
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Serge
authors.initials: S
authors.lastname: Jabbour
mesh_terms: D000368:Aged; D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000074099:Equivalence Trials as Topic; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D000069450:Liraglutide / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069450:Liraglutide; D008687:Metformin; D000077205:Pioglitazone; D045162:Thiazolidinediones; C000613158:IDegLira; C517652:hemoglobin A1c protein, human
keywords: efficacy; insulin therapy; randomized clinical trials; safety; type 2 diabetes