title: Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1).
abstract: OBJECTIVE
  To compare the efficacy and safety of dulaglutide, a once-weekly GLP-1 receptor agonist, with placebo and exenatide in type 2 diabetic patients. The primary objective was to determine superiority of dulaglutide 1.5 mg versus placebo in HbA1c change at 26 weeks.
  
  
  METHODS
  This 52-week, multicenter, parallel-arm study (primary end point: 26 weeks) randomized patients (2:2:2:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, exenatide 10 μg, or placebo (placebo-controlled period: 26 weeks). Patients were treated with metformin (1,500-3,000 mg) and pioglitazone (30-45 mg). Mean baseline HbA1c was 8.1% (65 mmol/mol).
  
  
  RESULTS
  Least squares mean ± SE HbA1c change from baseline to the primary end point was -1.51 ± 0.06% (-16.5 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, -1.30 ± 0.06% (-14.2 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, -0.99 ± 0.06% (-10.8 ± 0.7 mmol/mol) for exenatide, and -0.46 ± 0.08% (-5.0 ± 0.9 mmol/mol) for placebo. Both dulaglutide doses were superior to placebo at 26 weeks (both adjusted one-sided P < 0.001) and exenatide at 26 and 52 weeks (both adjusted one-sided P < 0.001). Greater percentages of patients reached HbA1c targets with dulaglutide 1.5 mg and 0.75 mg than with placebo and exenatide (all P < 0.001). At 26 and 52 weeks, total hypoglycemia incidence was lower in patients receiving dulaglutide 1.5 mg than in those receiving exenatide; no dulaglutide-treated patients reported severe hypoglycemia. The most common gastrointestinal adverse events for dulaglutide were nausea, vomiting, and diarrhea. Events were mostly mild to moderate and transient.
  
  
  CONCLUSIONS
  Both once-weekly dulaglutide doses demonstrated superior glycemic control versus placebo and exenatide with an acceptable tolerability and safety profile.
authors.affiliation: Redwood Clinic, Spokane, WA.
authors.forename: Carol
authors.initials: C
authors.lastname: Wysham
authors.affiliation: Texas Diabetes and Endocrinology, Austin, TX.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blevins
authors.affiliation: University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Richard
authors.initials: R
authors.lastname: Arakaki
authors.affiliation: American Telemedicine Center of Puerto Rico, San Juan, PR.
authors.forename: Gildred
authors.initials: G
authors.lastname: Colon
authors.affiliation: University Hospital Autonomous University of Nuevo León, Monterrey, Mexico.
authors.forename: Pedro
authors.initials: P
authors.lastname: Garcia
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN.
authors.forename: Charles
authors.initials: C
authors.lastname: Atisso
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN.
authors.forename: Debra
authors.initials: D
authors.lastname: Kuhstoss
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN lakshmanan_mark@lilly.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Lakshmanan
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D000077205:Pioglitazone; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D010455:Peptides; D011993:Recombinant Fusion Proteins; D045162:Thiazolidinediones; D014688:Venoms; D004763:Glucagon-Like Peptides; D008687:Metformin; D000077270:Exenatide; C555680:dulaglutide; D000077205:Pioglitazone