Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program

Abstract

Dulaglutide (DU) is a once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for the treatment of type 2 diabetes mellitus (T2DM). Glycaemic efficacy and safety characteristics of DU have been assessed in six Phase 3 studies in the AWARD program. The objective of this review article is to summarise these results from the 6 completed AWARD studies. At the primary endpoint, in 5 of the 6 studies, once weekly dulaglutide 1.5 mg was superior to the active comparator (exenatide, insulin glargine [two studies], metformin, and sitagliptin), with a greater proportion of patients reaching glycated haemoglobin A1c (HbA1c) targets of <7.0% (53.0 mmol/mol) and ≤6.5% (47.5 mmol/mol). Dulaglutide 1.5 mg was non-inferior to liraglutide in AWARD-6. Once weekly dulaglutide 0.75 mg was evaluated in 5 of these trials and demonstrated superiority to the active comparator in 4 of 5 AWARD studies (exenatide, glargine, metformin, and sitagliptin), and non-inferiority to glargine in the AWARD-2 study. Similar to other GLP-1 RAs, treatment with dulaglutide was associated with weight loss or attenuation of weight gain and low rates of hypoglycaemia when used alone or with non-insulin-secretagogue therapy. The most frequently reported adverse events were gastrointestinal, including nausea, diarrhoea, and vomiting. The incidence of dulaglutide antidrug antibody formation was 1%-2.8% with rare injection site reactions. In conclusion, dulaglutide is an effective treatment for T2DM and has an acceptable tolerability and safety profile.