title: Safety and efficacy of dulaglutide, a once weekly GLP-1 receptor agonist, for the management of type 2 diabetes.
abstract: BACKGROUND
  Type 2 diabetes (T2D) is an increasingly common endocrine disorder that is characterized by chronic hyperglycemia and tissue compartment abnormalities, including macrovascular and microvascular complications. More than 90% of patients with T2D will be diagnosed and treated in the primary care setting. One of the relatively recent additions to the increasing array of approved antidiabetic medications is the glucagon-like peptide-1 receptor agonist class. Mechanisms of action for glucagon-like peptide-1 receptor agonists include: 1) stimulation of insulin secretion through β-cells, though only when glucose levels are elevated (hence, minimizing risk for hypoglycemia); 2) blunting of glucagon secretion; 3) increased satiety; and 4) decreased rate of release of gastric contents into the small intestine, thereby reducing glycemic load. Recent T2D treatment guidelines encourage individualization of therapy. Many patients still do not achieve optimal glycemic control. Therefore, other treatment options are important.
  
  
  METHODS
  A literature search was performed using PubMed and MEDSCAPE to retrieve abstracts and articles pertinent to topics discussed in this review. Original research articles, reviews, and clinical trial manuscripts were identified based on relevance. Only English language articles were considered. Results In 3 phase 3 registration trials in patients with T2D, once-weekly dulaglutide demonstrated superior efficacy at the primary endpoint to metformin as monotherapy, to sitagliptin as add-on to metformin, and to exenatide twice daily as add-on to metformin and pioglitazone. The safety profile of dulaglutide in these trials is similar to currently available glucagon-like peptide-1 receptor agonists, characterized predominantly by gastrointestinal symptoms (ie, nausea, vomiting, and diarrhea). Based on these results, once-weekly dulaglutide should be a relevant additional treatment option for the management of T2D.
authors.affiliation: Department of Community Health and Family Medicine, University of Florida, Gainesville, FL.
authors.forename: Louis
authors.initials: L
authors.lastname: Kuritzky
authors.forename: Guillermo
authors.initials: G
authors.lastname: Umpierrez
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Ekoé
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mancillas-Adame
authors.forename: Laura Fernández
authors.initials: LF
authors.lastname: Landó
mesh_terms: D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D008687:Metformin / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage; D000077205:Pioglitazone; D011719:Pyrazines / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use; D014688:Venoms / Q000008:administration & dosage
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D010455:Peptides; D011719:Pyrazines; D018027:Receptors, Glucagon; D011993:Recombinant Fusion Proteins; D045162:Thiazolidinediones; D014230:Triazoles; D014688:Venoms; D004763:Glucagon-Like Peptides; D008687:Metformin; D000077270:Exenatide; D000068900:Sitagliptin Phosphate; C555680:dulaglutide; D000077205:Pioglitazone