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.

Abstract

AIMS:

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.

• Authors: R S Weinstock, B Guerci, G Umpierrez, M A Nauck, Z Skrivanek, Z Milicevic
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 17 Issue 9 Pg. 849-58 (Sep 2015) ISSN: 1463-1326 [Electronic] England
• PMID: 25912221 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Immunoglobulin Fc Fragments
• Recombinant Fusion Proteins
• hemoglobin A1c protein, human
• Glucagon-Like Peptides
• Metformin
• Sitagliptin Phosphate
• dulaglutide

Topics

• Blood Glucose (drug effects)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination (methods)
• Female
• Glucagon-Like Peptides (administration & dosage, analogs & derivatives)
• Glycated Hemoglobin (drug effects)
• Humans
• Hypoglycemic Agents (administration & dosage)
• Immunoglobulin Fc Fragments (administration & dosage)
• Male
• Metformin (administration & dosage)
• Middle Aged
• Recombinant Fusion Proteins (administration & dosage)
• Sitagliptin Phosphate (administration & dosage)
• Treatment Outcome
• Weight Loss (drug effects)