Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes (AWARD-5): a randomized, phase III study.
OBJECTIVE
To compare the once-weekly glucagon-like peptide-1 (GLP-1) receptor dulaglutide with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin after 104 weeks of treatment.


METHODS
This AWARD-5 study was a multicentre, double-blind trial that randomized participants to dulaglutide (1.5 or 0.75 mg) or sitagliptin 100 mg for 104 weeks or placebo (reported separately) for 26 weeks. Change in glycated haemoglobin (HbA1c) concentration from baseline was the primary efficacy measure. A total of 1098 participants with HbA1c concentrations ≥7.0% (≥53.0 mmol/mol) and ≤9.5% (≤80.3 mmol/mol) were randomized, and 657 (59.8%) completed the study. We report results for dulaglutide and sitagliptin at the final endpoint.


RESULTS
Changes in HbA1c at 104 weeks were (least squares mean ± standard error) -0.99 ± 0.06% (-10.82 ± 0.66 mmol/mol), -0.71 ± 0.07% (-7.76 ± 0.77 mmol/mol) and -0.32 ± 0.06% (-3.50 ± 0.66 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg and sitagliptin, respectively (p < 0.001, both dulaglutide doses vs sitagliptin). Weight loss was greater with dulaglutide 1.5 mg (p < 0.001) and similar with 0.75 mg versus sitagliptin (2.88 ± 0.25, 2.39 ± 0.26 and 1.75 ± 0.25 kg, respectively). Gastrointestinal adverse events were more common with dulaglutide 1.5 and 0.75 mg versus sitagliptin (nausea 17 and 15% vs 7%, diarrhoea 16 and 12% vs 6%, vomiting 14 and 8% vs 4% respectively). Pancreatic, thyroid, cardiovascular and hypersensitivity safety were similar across groups.


CONCLUSIONS
Dulaglutide doses provided superior glycaemic control and dulaglutide 1.5 mg resulted in greater weight reduction versus sitagliptin at 104 weeks, with acceptable safety.
Endocrinology, Diabetes and Metabolism, Upstate Medical University, Syracuse, NY, USA.
R S
RS
Weinstock
Diabetology, Metabolic Disease and Nutrition, University of Lorraine, CIC Inserm ILCV, CHU, Nancy, France.
B
B
Guerci
Diabetes & Endocrinology, Emory University, Atlanta, GA, USA.
G
G
Umpierrez
Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany.
M A
MA
Nauck
Lilly Research Laboratories, Indianapolis, IN, USA.
Z
Z
Skrivanek
Lilly Research Laboratories, Vienna, Austria.
Z
Z
Milicevic
D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage*; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D008687:Metformin; D011993:Recombinant Fusion Proteins; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human; C555680:dulaglutide
diabetes; dulaglutide; sitagliptin