title: Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial.
abstract: To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes.
  
  
  
  A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin.
  
  
  
  Mean baseline glycated hemoglobin (HbA1c) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6 mmol/mol]; 1.2 mg: -0.22% [2.4 mmol/mol]; 0.6 mg: -0.23% [2.5 mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis >1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01).
  
  
  
  In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
authors: Lund University, Lund, Sweden bo.ahren@med.lu.se.
authors: Bo
authors: B
authors: Ahrén
authors: University of Washington, Seattle, WA.
authors: Irl B
authors: IB
authors: Hirsch
authors: Medical University of Graz, Graz, Austria.
authors: Thomas R
authors: TR
authors: Pieber
authors: University of Leuven, Leuven, Belgium.
authors: Chantal
authors: C
authors: Mathieu
authors: Hospital General de Segovia, Segovia, Spain.
authors: Fernando
authors: F
authors: Gómez-Peralta
authors: Aarhus University Hospital, Aarhus, Denmark.
authors: Troels Krarup
authors: TK
authors: Hansen
authors: University of Cape Town Private Academic Hospital, Cape Town, South Africa.
authors: Areti
authors: A
authors: Philotheou
authors: Novo Nordisk A/S, Bagsvaerd, Denmark.
authors: Sune
authors: S
authors: Birch
authors: Novo Nordisk A/S, Bagsvaerd, Denmark.
authors: Erik
authors: E
authors: Christiansen
authors: Novo Nordisk A/S, Bagsvaerd, Denmark.
authors: Thomas Jon
authors: TJ
authors: Jensen
authors: University of North Carolina School of Medicine, Chapel Hill, NC.
authors: John B
authors: JB
authors: Buse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; 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; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide