Dulaglutide: A GLP-1 Receptor Agonist for Once Weekly Treatment of Type 2 Diabetes

Introduction: Dulaglutide is one of the most recent glucagon-like peptide 1 (GLP-1) receptor agonists and has been approved for once weekly injection in the treatment of type 2 diabetes. The efficacy and safety of dulaglutide have been shown in currently 7 published phase-3 studies of the AWARD study program. Methods: This review summarizes the efficacy and safety results of the published AWARD studies and discusses the role of dulaglutide once weekly in the context of the GLP-1 receptor agonist class and other possible treatment options in type 2 diabetes. Results: The AWARD studies had a total of 5470 patients, including 3375 patients treated with dulaglutide once weekly, and show the efficacy and safety of dulaglutide in combination with metformin and/ or other antihyperglycemic treatments, as well as in monotherapy. In 6 of the 7 studies (AWARD-1-5, AWARD-8), the decrease in HbA(1c) achieved with the 1.5mg standard dose of dulaglutide commonly used in Germany was superior to the respective comparator used (exenatide twice daily, insulin glargine, metformin, sitagliptin) or placebo. In the AWARD-6 study, dulaglutide 1.5mg once weekly was the first weekly GLP-1 receptor agonist shown to be non-inferior to liraglutide 1.8mg injected once daily. As with all GLP-1 receptor agonists, nausea, diarrhea and vomiting usually occurring during the first 2 weeks of treatment - were the most common adverse effects. Hypoglycemia rates were low, and in all studies at primary study endpoint a mean weight reduction of approximately 1-3 kg was observed with the 1.5mg dose. When looking at a combined endpoint (HbA(1c) < 7 % with no hypoglycemia or weight gain), dulaglutide was associated with a more advantageous benefit risk profile compared with exenatide twice daily or insulin glargine; in indirect, comparative "bridging" analyses this was also the case for the comparison against sulfonylureas. Conclusions: The efficacy and safety profile, together with once-weekly administration, make dulaglutide a relevant treatment option within the class of GLP-1 receptor agonists. Treatment decisions for type 2 diabetes, in particular when transitioning to injectable antihyperglycemic treatment, increasingly consider patients' specific requirements, comorbidities and preferences in addition to the adjustment of glycemic control as per guidelines. Each GLP-1 receptor agonist should therefore be considered individually, due to the differences between these agents.