Incretin therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors

Abstract

Incretin therapy is a glucose‐lowering therapy which has attracted great interest during recent years. It is based on the antidiabetic action of the incretin hormone glucagon‐like peptide‐1 (GLP‐1), which involves both stimulation of insulin secretion and inhibition of glucagon secretion. This results in lowering of both fasting and postprandial glycaemia. Incretin therapy is either with GLP‐1 receptor agonists or with inhibitors of dipeptidyl peptidase‐4 (DPP‐4), which is the enzyme which inactivates endogenous GLP‐1. The GLP‐1 receptor agonists are injected subcutaneously once or twice daily or once weekly. The DPP‐4 inhibitors are oral tablets taken once or twice daily. Both therapies reduce HbA1c without weight gain, and for GLP‐1 receptor agonists with a weight reduction. Incretin therapy is safe with very few adverse events and an additional value of the therapy is a very low risk for hypoglycaemia. Incretin therapy is efficient both in monotherapy and in combination with metformin, sulphonylureas, thiazolidinediones and insulin. Its main indication is as add‐on to metformin in patients who are insufficiently controlled on metformin alone, and an important indication is also in combination with insulin therapy. The experienced value of incretin therapy for patient care will most likely result in increased use of this therapy during the coming years. Copyright © 2013 FEND. Published by John Wiley & Sons, Ltd.

GLP-1 receptor agonists in the treatment of Type 2 diabetes

“…Therefore, there are similarities between the GLP-1 receptor agonists and DPP-4 inhibitors, for example, both target the islet dysfunction in Type 2 diabetes by stimulating insulin secretion and inhibiting glucagon secretion, as well as efficiently reducing HbA1c with a very low risk of hypoglycemia [54]. There are, however, also differences between the two strategies.…”

Insulin plus incretin: A glucose-lowering strategy for type 2-diabetes

“…In the early development of GLP-1 as a therapy, GLP-1 had to be given as an intravenous infusion since the hormone is rapidly inactivated by DPP-4 [16] . The two successful strategies for incretin therapy used this knowledge and today we have several GLP-1 receptor agonists which are not or only weakly inactivated by DPP-4 and DPP-4 inhibitors [17][18][19][20] .…”

Combined insulin detemir and liraglutide therapy in type 2 diabetic patients: a base for an alliance

“…Наиболее частыми побочными эффектами на фоне при-менения аГПП-1Р являются гастроинтестинальные явления (тошнота, рвота, диарея), обычно возникаю-щие в начале применения аГПП-1Р, слабо выраженные и, как правило, транзиторного характера [15,44].…”

“…С учетом короткого периода полужизни нативного ГПП-1 разработаны две успешные стратегии инкрети-новой терапии: увеличение концентрации ГПП-1 с по-мощью препаратов экзогенного аГПП-1Р, устойчивых к деградации ДПП-4, и повышение устойчивости эндо-генного ГПП-1 путем замедления его деградации с помо-щью иДПП-4 [15]. Агонисты ГПП-1Р вводятся подкожно 1 или 2 раза в день (эксенатид, лираглутид, ликсисена-тид) либо 1 раз в неделю (пролонгированная форма эксенатида, дулаглутид, албиглутид, семаглутид [16]).…”

“…Принципиально важно, что применение инкретино-вых препаратов позволяет снижать уровни как гликемии натощак, так и постпрандиальной при низком риске ги-погликемии и отсутствии негативного влияния на массу тела (снижение массы тела либо нейтральное влияние на вес) [15].…”