Efficacy and Safety of Dulaglutide Versus Sitagliptin After 52 Weeks in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-5)
Top Cited Papers
Open Access
- 12 July 2014
- journal article
- research article
- Published by American Diabetes Association in Diabetes Care
- Vol. 37 (8), 2149-2158
- https://doi.org/10.2337/dc13-2761
Abstract
OBJECTIVE To compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks. RESEARCH DESIGN AND METHODS This multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented. RESULTS The mean HbA1c changes to 52 weeks were (least squares mean ± SE): −1.10 ± 0.06% (−12.0 ± 0.7 mmol/mol), −0.87 ± 0.06% (9.5 ± 0.7 mmol/mol), and −0.39 ± 0.06% (4.3 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (−3.03 ± 0.22 kg) and dulaglutide 0.75 mg (−2.60 ± 0.23 kg) compared with sitagliptin (−1.53 ± 0.22 kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting. CONCLUSIONS Both dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.Keywords
This publication has 39 references indexed in Scilit:
- Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered ApproachDiabetes Care, 2012
- LY2189265, a long-acting glucagon-like peptide-1 analogue, showed a dose-dependent effect on insulin secretion in healthy subjectsDiabetes, Obesity and Metabolism, 2011
- Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trialThe Lancet, 2010
- Engineering and characterization of the long‐acting glucagon‐like peptide‐1 analogue LY2189265, an Fc fusion proteinDiabetes/Metabolism Research and Reviews, 2010
- Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trialThe Lancet, 2010
- Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD)Diabetes Care, 2009
- Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 DiabetesDiabetes Care, 2009
- The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetesThe Lancet, 2006
- The Glucagon-Like PeptidesEndocrine Reviews, 1999
- Truncated glucagon‐like peptide I, an insulin‐releasing hormone from the distal gutFEBS Letters, 1987