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Dulaglutid

Publication at Second Faculty of Medicine |
2016

Abstract

Dulaglutide is a new long-acting glucagon-like peptide-1 receptor agonist (GLP-1 agonist). It consists of two molecules of GLP-1 analog (90% homology with human GLP-1) covalently linked (by two peptides) to an Fc fragment of human IgG4.

The basic dosage in type 2 diabetes mellitus is 0.75 mg for monotherapy and 1.5 mg for add-on therapy once weekly; the biological half-life is 4.7 days. Its prolonged effect is a result of slowed absorption from a subcutaneous deposit, lowered renal clearance, and slowed breakdown of the molecule by dipeptidyl peptidase 4.

Steady-state plasmatic concentration is being reached after 2-4 weeks of application. Dulaglutide lowers both fasting and postprandial glycemia, improves insulin secretion, lowers glucagon secretion, and reduces both appetite and body weight.

It also lowers systolic blood pressure (by -2.8 mm Hg). Effectiveness and safety of dulaglutide administration were compared with those of liraglutide administration in the AWARD-6 trial.

Treatment with 1.8 mg liraglutide lead to glycated hemoglobin (HbA1c) concentration decrease by 1.36% (DCCT) while treatment with 1.5 mg dulaglutide reduced HbA1c concentration by 1.42%. Non-inferiority criteria were thus met.

Liraglutide treatment was associated with more pronounced weight reduction (by 0.71 kg on average, p = 0.011). The incidence of adverse effects was identical.

The most common (and expected) adverse effects of dulaglutide therapy are nausea and other dyspeptic symptoms, usually abating after several applications. Discontinuation of therapy because of these adverse effects is required only exceptionally.

Available scientific work shows that dulaglutide will be well tolerated and his effectiveness will be equal to that of liraglutide, the major advantage being represented by once weekly application.