title: Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5.
abstract: OBJECTIVE
  To investigate the efficacy and tolerability of albiglutide, a weekly glucagon-like peptide-1 receptor agonist, when added to metformin and glimepiride in a triple therapy regimen in people with type 2 diabetes mellitus.
  
  
  METHODS
  This was a 156-week, randomized, double-blind, parallel-group, multicentre study. In the present paper we describe the primary results, namely those at 52 weeks. Adult participants (n = 685) were randomly assigned to albiglutide (30 mg/week), pioglitazone (30 mg/day) or placebo. If needed, blinded uptitration of albiglutide (to 50 mg/week) and pioglitazone (to 45 mg/day) was allowed. The participant's current dose of metformin (>1500 mg/day) was maintained throughout. The glimepiride dose (4 mg/day), standardized before randomization, could be decreased if persistent hypoglycaemia occurred.
  
  
  RESULTS
  The week 52 model-adjusted difference in change of glycated haemoglobin (primary endpoint) for albiglutide versus placebo was -0.87 [95% confidence interval (CI) -1.07, -0.68]%-units (p < 0.001), and for albiglutide versus pioglitazone it was 0.25 (95% CI 0.10, 0.40)%-units; therefore, not non-inferior. In the albiglutide group only, fasting plasma glucose reduced rapidly in the first 2 weeks. Confirmed hypoglycaemia occurred in 14% of participants on albiglutide, 25% on pioglitazone and 14% on placebo. The mean (± standard error) weight change was -0.42 (±0.2) kg with albiglutide, +4.4 (±0.2) kg (p < 0.001) with pioglitazone, and -0.40 (±0.4) kg with placebo and serious adverse events occurred in 6.3, 9.0 and 6.1% of participants in the respective groups. Injection site reactions occurred in 13% of participants on albiglutide and resulted in treatment discontinuation for four participants (1.4%).
  
  
  CONCLUSIONS
  Albiglutide, as part of triple therapy, provided effective glucose-lowering and was generally well tolerated.
authors.affiliation: Institute of Cellular Medicine-Diabetes, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: P D
authors.initials: PD
authors.lastname: Home
authors.forename: P
authors.initials: P
authors.lastname: Shamanna
authors.forename: M
authors.initials: M
authors.lastname: Stewart
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Miller
authors.forename: C
authors.initials: C
authors.lastname: Perry
authors.forename: M C
authors.initials: MC
authors.lastname: Carr
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C534611:rGLP-1 protein; C057619:glimepiride
keywords: albiglutide; glucagon-like peptide-1 receptor agonist; pioglitazone; type 2 diabetes mellitus