title: Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes.
abstract: OBJECTIVE
  Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years.
  
  
  METHODS
  Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia.
  
  
  RESULTS
  For patients completing 2 years of therapy, HbA1c reductions were -0.6% with glimepiride versus -0.9% with liraglutide 1.2 mg (difference: -0.37, 95% CI: -0.71 to -0.02; p = 0.0376) and -1.1% with liraglutide 1.8 mg (difference: -0.55, 95% CI: -0.88 to -0.21; p = 0.0016). In the ITT population, HbA1c reductions were -0.3% with glimepiride versus -0.6% with liraglutide 1.2 mg (difference: -0.31, 95% CI: -0.54 to -0.08; p = 0.0076) and -0.9% with liraglutide 1.8 mg (difference: -0.60, 95% CI: -0.83 to -0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001).
  
  
  CONCLUSIONS
  Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.
authors.affiliation: Department of Medicine and the Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine, 1709 Dryden Road, Houston, TX 77030, USA. agarber@bcm.tmc.edu
authors.forename: A
authors.initials: A
authors.lastname: Garber
authors.forename: R R
authors.initials: RR
authors.lastname: Henry
authors.forename: R
authors.initials: R
authors.lastname: Ratner
authors.forename: P
authors.initials: P
authors.lastname: Hale
authors.forename: C T
authors.initials: CT
authors.lastname: Chang
authors.forename: B
authors.initials: B
authors.lastname: Bode
mesh_terms: D001786:Blood Glucose / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D013453:Sulfonylurea Compounds; C057619:glimepiride