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Publication Type : Journal Article
Thematic Areas : Medical Sciences
Publisher : Journal of Association of Physicians of India
Source : Journal of Association of Physicians of India, Volume 58, Number SPEC. ISSUE, p.10-14 (2010)
Campus : Kochi
School : School of Medicine
Department : Endocrinology
Year : 2010
Abstract : A set of physiological responses is activated following meal intake, providing neural and endocrine signals regulating the digestion, absorption and assimilation of ingested nutrients, in which incretin plays an important role. It is believed that the incretin effect is mediated mainly by two incretin hormones: gastric inhibitory polypeptide (GIP) and glucagon-like peptides (GLP)-1. Shortly following release from gut L cells, GLP-1 is rapidly degraded by dipeptide peptidase-4 (DPP-4) to GLP-1(9-36) or GLP-1(9-37) amide, which inactivates native GLP-1. Because of the short plasma half-life of native GLP-1, about 2 minutes, long-acting derivatives should be developed to make GLP-1 treatment therapeutically relevant. It has been demonstrated that DPP-4 inhibition can protect GLP-1 and GIP from degradation, resulting in enhanced insulinotropic activity of infused GLP. Currently, DPP-4 inhibitors on the market are mainly sitagliptin and vildagliptin. Both inhibitors have significant antidiabetic effects when given in monotherapy and can result in further improvements in glycaemic control when given in combination with other antidiabetic agents such as metformin, sulfonylurea (SU) and thiazolidinediones (TZDs). Exenatide is the first GLP-1 receptor agonist that has been approved for use as an adjunctive therapy to improve glycaemic control in patients with type 2 diabetes who are not adequately controlled with metformin/ SU mono- or combination therapy. Liraglutide is the first once-daily human GLP-1 analogue. In July 2009, Victoza® (liraglutide) was approved by the European Medicines Agency (EMA) in the treatment of type 2 diabetes mellitus to achieve glycaemic control. In January 2010, the U.S. Food and Drug Association (FDA) approved Victoza® as an adjunct therapy to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus. It has been shown in different trials that at suggested therapeutic doses of 1.2 mg and 1.8 mg, liraglutide can lower glycated haemoglobin A1c (HbA1c) by 1.0-1.5% points as mono- or combination therapy in approximately two-thirds of subjects. GLP-1 receptor agonist showed a greater effect than the DPP-4 inhibitor in reducing postprandial glucose (PPG) concentrations, a more potent effect in increasing insulin secretion and decreasing postprandial glucagon secretion, a relatively greater effect in reducing caloric intake, and it decreased the rate of gastric emptying. Overall, available evidence supports the use of incretin-based therapies in diabetes patients requiring effective glycaemic and body weight control while minimising the risk of hypoglycaemia. © SUPPLEMENT TO JAPI.
Cite this Research Publication : Aa Bhansali, Maji, Db, Rao, P. Vc, Banerjee, Sb, and Kumar, Hd, “Historical overview of incretin based therapies”, Journal of Association of Physicians of India, vol. 58, pp. 10-14, 2010.