title: Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial.
abstract: OBJECTIVE
  To confirm the superiority, compared with placebo, of adding liraglutide to pre-existing basal insulin analogue ± metformin in adults with inadequately controlled type 2 diabetes [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)].
  
  
  METHODS
  In this 26-week, double-blind, parallel-group study, conducted in clinics or hospitals, 451 subjects were randomized 1 : 1 to once-daily liraglutide 1.8 mg (dose escalated from 0.6 and 1.2 mg/day, respectively, for 1 week each; n = 226) or placebo (n = 225) added to their pre-existing basal insulin analogue (≥20 U/day) ± metformin (≥1500 mg/day). After randomization, insulin adjustments above the pre-study dose were not allowed. The primary endpoint was HbA1c change.
  
  
  RESULTS
  After 26 weeks, HbA1c decreased more with liraglutide [-1.3% (-14.2 mmol/mol)] than with placebo [-0.1% (-1.2 mmol/mol); p < 0.0001]. More subjects on liraglutide reached HbA1c targets: <7.0% (59% vs 14%; p < 0.0001) and ≤6.5% (43% vs 4%; p < 0.0001) using slightly less insulin (35.8 IU vs 40.1 IU). Greater decreases from baseline (estimated treatment differences vs placebo; p < 0.0001) occurred in fasting plasma glucose (-1.3 mmol/l), seven-point glucose profiles (-1.6 mmol/l), body weight (-3.1 kg) and systolic blood pressure (-5.0 mmHg). Transient gastrointestinal adverse events (nausea: 22.2% vs 3.1%) and minor hypoglycaemia (18.2% vs 12.4%) were more frequent with liraglutide than placebo, and pulse increased (4.5 beats/min) compared with placebo. No severe hypoglycaemia or pancreatitis occurred.
  
  
  CONCLUSIONS
  Adding liraglutide to a basal insulin analogue ± metformin significantly improved glycaemic control, body weight and systolic blood pressure compared with placebo. Typical gastrointestinal symptoms and minor hypoglycaemia were more frequent with liraglutide.
authors.affiliation: Oregon Health and Science University, Portland, OR, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ahmann
authors.affiliation: Endocrine and Metabolic Consultants, Rockville, MD, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Rodbard
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: University Hospital, Tampere University, Tampere, Finland.
authors.forename: J T
authors.initials: JT
authors.lastname: Lahtela
authors.affiliation: Servicio Diabetología y Nutrición, Hospital Privado de Córdoba S.A., Córdoba, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: de Loredo
authors.affiliation: Medical and Science, GLP-1 and Obesity, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Tornøe
authors.affiliation: Novo Nordisk Service Centre, India Pvt Ltd, Bangalore, India.
authors.forename: A
authors.initials: A
authors.lastname: Boopalan
authors.affiliation: Division of Diabetology, Medical Department I, St. Josef-Hospital (Ruhr-Universität Bochum), Bochum, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Nauck
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D061385:Insulins / Q000008:administration & dosage*; D000069450:Liraglutide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061385:Insulins; D000069450:Liraglutide; D008687:Metformin; C517652:hemoglobin A1c protein, human
keywords: GLP-1 analogue; glycaemic control; incretin therapy; insulin therapy; randomised trial; weight loss therapy