title: Albiglutide for the treatment of type 2 diabetes mellitus: An integrated safety analysis of the HARMONY phase 3 trials.
abstract: OBJECTIVE
  Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stimulate the incretin system and lower glycaemic parameters in type 2 diabetes mellitus (T2DM). This analysis of clinical studies of up to 3years evaluated the safety of albiglutide, a GLP-1 RA, in people with T2DM.
  
  
  METHODS
  Integrated safety analysis included seven phase-3 T2DM studies of albiglutide compared with placebo and/or active comparators (a dipeptidyl peptidase-4 inhibitor, GLP-1 RA, insulin, sulphonylurea, and thiazolidinedione).
  
  
  RESULTS
  Studies of 32months (HARMONY 7), 1year (HARMONY 6), and 3years (HARMONY 1-5), reported similar rates of adverse events (AEs) (84.8%, 82.3%), and serious AEs (13.1%, 12.9%) between albiglutide and all comparators, respectively. AEs that did not differ between the groups included symptomatic or severe hypoglycaemia as well as nausea (12.0%, 11.3%) and vomiting (5.3%, 4.7%) for albiglutide and all comparators, respectively. According to the Medical Dictionary for Regulatory Activities preferred terms, only diarrhoea (13.7%, 9.9%), injection-site reaction (9.0%, 2.0%), and peripheral oedema (4.5%, 6.8%) had at least 2% difference between the albiglutide and all-comparator groups. In a similar integrated analysis, pancreatitis occurred more often with albiglutide (0.3%, 0.1%). Renal and cardiac function did not differ between the two groups.
  
  
  CONCLUSIONS
  In an integrated analysis of seven phase 3 clinical trials, albiglutide-treated patients experienced frequencies of AEs (including cardiovascular and renal) similar to the all-comparators group treated with other T2DM medications or placebo. Albiglutide treatment was associated with higher rates of diarrhoea and injection-site reactions, but not increased nausea and vomiting, versus all comparators.
authors.affiliation: Department of Clinical Services Division of Medicine, Lund University, Lund, Sweden. Electronic address: Bo.Ahren@med.lu.se.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.affiliation: Pharma Research & Development, GlaxoSmithKline, Collegeville, PA, USA. Electronic address: molly.c.carr@gsk.com.
authors.forename: Molly C
authors.initials: MC
authors.lastname: Carr
authors.affiliation: Pharma Research & Development, GlaxoSmithKline, Collegeville, PA, USA. Electronic address: Karen.J.Murphy@gsk.com.
authors.forename: Karen
authors.initials: K
authors.lastname: Murphy
authors.affiliation: PPD, Inc, Morrisville, NC, USA. Electronic address: christopher.perkins@ppdi.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Perkins
authors.affiliation: Department of Medicine, Division of Endocrinology, Creighton University, Omaha, NE, USA. Electronic address: rendell@asndi.com.
authors.forename: Marc
authors.initials: M
authors.lastname: Rendell
authors.affiliation: Pharma Research & Development, GlaxoSmithKline, Upper Merion, PA, USA. Electronic address: jasonmallory@hotmail.com.
authors.forename: Jason
authors.initials: J
authors.lastname: Mallory
authors.affiliation: Pharma Research & Development, R&D Projects Clinical Platforms, PCPS Qsci Clinical Statistics, Research Triangle Park, Durham, NC, USA. Electronic address: Tim.Wilson@parexel.com.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilson
authors.affiliation: Pharma Research & Development, GlaxoSmithKline, Upper Merion, PA, USA. Electronic address: Susan.l.johnon@pfizer.com.
authors.forename: Susan
authors.initials: S
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use; D007267:Injections / Q000009:adverse effects; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D013453:Sulfonylurea Compounds; C534611:rGLP-1 protein; D052216:Glucagon-Like Peptide 1
keywords: Diabetes mellitus; Glucagon-like peptide-1; Incretins; Long-term safety