Dulaglutide (LY-2189265) for the treatment of type 2 diabetes

ABSTRACT

Dulaglutide is a new once-weekly glucagon-like peptide-1 receptor agonist for the management of hyperglycemia in adult patients with type 2 diabetes. It stimulates dose-dependent insulin secretion and reduces glucagon secretion, both in a glucose-dependent manner. Efficacy on blood glucose control and safety were demonstrated in the large AWARD program in type 2 diabetic patients treated with diet, metformin, dual oral therapy or insulin lispro with or without metformin, confirming findings of pilot studies in Caucasian patients and data in Japanese patients. Dulaglutide 1.5 mg once weekly was superior to metformin, sitagliptin, insulin glargine and exenatide twice daily, and non-inferior to liraglutide 1.8 mg once daily regarding the reduction in glycated hemoglobin. A modest but significant weight loss was consistently observed. Most frequent adverse events were transient and generally mild gastrointestinal disturbances. Clinical outcomes of dulaglutide will not be known until the large prospective cardiovascular outcome trial REWIND is complete.

KEYWORDS:

• Dulaglutide
• Clinical trial
• GLP-1 receptor agonist
• Insulin secretion
• Once weekly injection
• Therapy
• Type 2 diabetes mellitus

Financial and competing interests disclosure

A.J. Scheen has received lecture/advisor/investigator fees from AstraZeneca/BMS, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novartis, NovoNordisk, Sanofi and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Incretin-based therapies, including GLP-1 receptor agonists, occupy a growing place in the management of T2DM.

• Dulaglutide is a new human GLP-1 receptor agonist designed to be injected once weekly at a dose of 0.75–1.50 mg in Caucasian patients (lower doses in Japanese patients).

• Dulaglutide reduces both fasting and postprandial glucose, mainly by stimulating insulin secretion and reducing glucagon secretion in a glucose-dependent manner, thus with a low risk of hypoglycemia.

• Dulaglutide has been evaluated in the AWARD program, mainly in Caucasian people, and the efficacy and safety results were confirmed in several trials performed in Japanese patients.

• Dulaglutide has proven its efficacy in reducing HbA1c in T2DM patients treated with diet alone, metformin, dual oral therapy (metformin plus sulfonylurea or metformin plus pioglitazone) and even lispro insulin.

• Dulaglutide 1.5 mg once weekly is more potent than metformin, exenatide, insulin glargine (if not forced titrated to target), and as effective as liraglutide 1.8 mg once daily.

• Dulaglutide has the same tolerance and safety profile as other GLP-1 RAs, with transient gastrointestinal disturbances as most frequent adverse events.

• Dulaglutide is currently evaluated in a large, prospective, cardiovascular outcome trial (REWIND) whose results are not awaited before 2019.