title: Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial.
abstract: To investigate whether liraglutide added to treat-to-target insulin improves glycemic control and reduces insulin requirements and body weight in subjects with type 1 diabetes.
  
  
  
  A 52-week, double-blind, treat-to-target trial involving 1,398 adults randomized 3:1 to receive once-daily subcutaneous injections of liraglutide (1.8, 1.2, or 0.6 mg) or placebo added to insulin.
  
  
  
  HbA1c level was reduced 0.34-0.54% (3.7-5.9 mmol/mol) from a mean baseline of 8.2% (66 mmol/mol), and significantly more for liraglutide 1.8 and 1.2 mg compared with placebo (estimated treatment differences [ETDs]: 1.8 mg liraglutide -0.20% [95% CI -0.32; -0.07]; 1.2 mg liraglutide -0.15% [95% CI -0.27; -0.03]; 0.6 mg liraglutide -0.09% [95% CI -0.21; 0.03]). Insulin doses were reduced by the addition of liraglutide 1.8 and 1.2 mg versus placebo (estimated treatment ratios: 1.8 mg liraglutide 0.92 [95% CI 0.88; 0.96]; 1.2 mg liraglutide 0.95 [95% CI 0.91; 0.99]; 0.6 mg liraglutide 1.00 [95% CI 0.96; 1.04]). Mean body weight was significantly reduced in all liraglutide groups compared with placebo ETDs (1.8 mg liraglutide -4.9 kg [95% CI -5.7; -4.2]; 1.2 mg liraglutide -3.6 kg [95% CI -4.3; -2.8]; 0.6 mg liraglutide -2.2 kg [95% CI -2.9; -1.5]). The rate of symptomatic hypoglycemia increased in all liraglutide groups (estimated rate ratios: 1.8 mg liraglutide 1.31 [95% CI 1.07; 1.59]; 1.2 mg liraglutide 1.27 [95% CI 1.03; 1.55]; 0.6 mg liraglutide 1.17 [95% CI 0.97; 1.43]), and hyperglycemia with ketosis increased significantly for liraglutide 1.8 mg only (event rate ratio 2.22 [95% CI 1.13; 4.34]).
  
  
  
  Liraglutide added to insulin therapy reduced HbA1c levels, total insulin dose, and body weight in a population that was generally representative of subjects with type 1 diabetes, accompanied by increased rates of symptomatic hypoglycemia and hyperglycemia with ketosis, thereby limiting clinical use in this group.
authors: Gasthuisberg Hospital, University of Leuven, Leuven, Belgium chantal.mathieu@med.kuleuven.be.
authors: Chantal
authors: C
authors: Mathieu
authors: Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: Bernard
authors: B
authors: Zinman
authors: Capio St. Görans Hospital and the Karolinska Institute, Stockholm, Sweden.
authors: Joanna Uddén
authors: JU
authors: Hemmingsson
authors: Health Sciences Centre, Winnipeg, Manitoba, Canada.
authors: Vincent
authors: V
authors: Woo
authors: Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors: Peter
authors: P
authors: Colman
authors: Novo Nordisk A/S, Bagsværd, Denmark.
authors: Erik
authors: E
authors: Christiansen
authors: Novo Nordisk A/S, Bagsværd, Denmark.
authors: Martin
authors: M
authors: Linder
authors: Atlanta Diabetes Associates, Atlanta, GA.
authors: Bruce
authors: B
authors: Bode
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage; D000069450:Liraglutide / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide