title: Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.
abstract: OBJECTIVE
  Additional safe and effective therapies for type 2 diabetes are needed, especially ones that do not cause weight gain and have a low risk of hypoglycaemia. The present study evaluated albiglutide as monotherapy.
  
  
  METHODS
  In this placebo-controlled study, 309 patients (aged ≥ 18 years) with type 2 diabetes inadequately controlled by diet and exercise and who were not using a glucose-lowering agent (HbA1c 7.0-10.0% [53.00-85.79 mmol/mol], body mass index 20-45 kg/m(2), and fasting C-peptide ≥ 0.26 nmol/l) were randomised (1:1:1 on a fixed randomisation schedule using an interactive voice response system) to receive once-weekly albiglutide 30 mg (n = 102) or 50 mg (n = 102) or matching placebo (n = 105). The study treatments were blinded to both patients and study personnel. All study data were collected at individual patient clinic visits. The primary efficacy endpoint was change in HbA1c from baseline to week 52. The primary analysis was applied to the intent-to-treat population. Additional efficacy and safety endpoints were assessed.
  
  
  RESULTS
  At week 52, both albiglutide 30 mg and 50 mg were superior to placebo in reducing HbA1c. The least-squares means treatment difference from placebo was -0.84% (95% CI -1.11%, -0.58%; p < 0.0001) with albiglutide 30 mg and -1.04% (-1.31%, -0.77%; p < 0.0001) with albiglutide 50 mg. Injection-site reactions were reported more frequently with albiglutide (30 mg: 17.8%; 50 mg: 22.2%) than with placebo (9.9%). Other commonly reported adverse events included nausea, diarrhoea, vomiting and hypoglycaemia; the incidences of these were generally similar across treatment groups.
  
  
  CONCLUSIONS
  Albiglutide is safe and effective as monotherapy and significantly lowered HbA1c levels over 52 weeks, did not cause weight gain, and had good gastrointestinal tolerability and a low rate of hypoglycaemia compared with placebo. Trial registration ClinicalTrials.gov NCT00849017 Funding This study was sponsored by GlaxoSmithKline.
authors.affiliation: St Josef Hospital (Ruhr-Universität Bochum), Gudrunstr. 56, D-44791, Bochum, Germany. michael.nauck@rub.de.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Murray W
authors.initials: MW
authors.lastname: Stewart
authors.affiliation: PPD Inc., Morrisville, NC, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Perkins
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Jones-Leone
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Yang
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Perry
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Rickey R
authors.initials: RR
authors.lastname: Reinhardt
authors.affiliation: Creighton University, Omaha, NE, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Rendell
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000628:therapy; D004032:Diet; D015444:Exercise / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D015415:Biomarkers; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C534611:rGLP-1 protein
keywords: Albiglutide; GLP-1 agonist; Randomised controlled trial; Type 2 diabetes