Effects of Incretin Mimetic Drugs on Diabetic Cardiovascular Functions

Headnote

Effects of Incretin Mimetic Drugs on Diabetic Cardiovascular Functions

SUMMARY

Incretin effect has a key role in glycemic homeostasis following meals. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for the incretin effect; they are released from the small intestine after meals and stimulate insulin secretion from pancreatic ß-cells, thereby causing significant reduction in blood sugar level. These peptides have quite short half-lives, as they are inactivated within minutes by the enzyme dipeptidyl peptidase (DPP-4). In type 2 diabetes mellitus (T2DM), GLP-1 levels decrease, and incretin effect is reduced. This worsens the diabetic state. Two different groups of drugs, GLP-1 receptor agonists and DPP-4 inhibitors, have been developed in order to benefit from the favorable effects of GLP-1 on glucose homeostasis, and they have been since used in treatment of T2DM. Both groups of drugs show favorable effects on cardiovascular dysfunctions, independent of their blood glucose-lowering effects, and thisfeature distinguishes them from the conventional anti-hyperglycemic agents. Preclinical and clinical studies have shown that both GLP-1 receptor activation and DPP-4 inhibition exert multifaceted cardioprotection on cardiovascular dysfunction. In addition to providing glycemic control, treatment with incretin mimetic drugs help to control body weight, significantly reduce the risk of hypoglycemia, lower blood pressure and improve cardiovascular functions. Furthermore, by increasing the number of pancreatic ß-cells, they ameliorate the pancreatic injury caused by diabetes and enhance insulin response. Considering all these benefits together, incretin mimetic drugs have been proposed as first-line medications in combined therapy of diabetic patients, especially in the presence of cardiovascular complications.

Key Words: Diabetes, Cardiovascular, Antidiabetic, Incretin, GLP-1, DPP-4.

İnkretin Mimetik İlaçların Diabetik Kardiyovasküler Fonksiyonlar Üzerindeki Etkileri

ÖZET

Inkretin etki, yemek sonrası glisemik homeostaztn sağlanmasında etkin rol oynayan bir mekanizmadır. inkretin etkiden sorumlu Glukagon benzeri peptid-1 (GLP-1) ve Glukoz-bağımlı insülinotropik polipeptid (GIP), yemek sonrası ince bağırsaktan salgılanarak pankreasın ß-hücrelerinden insülin sekresyonunu arttırırlar, böylece kan şekerini belirgin olarak düşürürler. Söz konusu peptidler dakikalar içerisinde dipeptidil peptidaz enzimi (DPP-4) tarafından inaktive edildiklerinden yarılanma ömürleri oldukça kısadır. T2DMde GLP-1 seviyeleri düşer ve inkretin etki azalır. Bu durum diyabet tablosunu daha da kötüleştirir. GLP-1 ·in glukoz dengesi üzerindeki olumlu etkilerinden yararlanmak için iki farklı ilaç grubu geliştirilmiş ve Tip 2 diyabet tedavisinde kullanılmaya başlanmıştır; GLP-1 reseptör agonistleri ve DPP-4 inhibitörleri. Her iki grup da kan...