Folia Medica Indonesiana
ISSN 0303-7932
Vol. 45 / No. 3 / Published : 2009-07
Order : 13, and page :237 - 243
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Original Article :
Review article and clinical experiences: a novel oad with broadspeactrum therapeutic value for pts with t2dm the roles of galvus® for pts with t2dm, mody,txdm, pre-dm, and t1dm
Author :
- Askandar Tjokroprawiro*1
- Diabetes and Nutrition Center – Dr. Soetomo Teaching Hospital Faculty of Medicine, Airlangga University Surabaya
Abstract :
Incretins, or gut hormones (glucagon-like peptide-1 = GLP-1, and glucose-dependent insulinotropic polypeptide = GIP), exert several beneficial effects in glycemic control, collectively called the “incretin effect”. It is refers to the amplification of the insulin response to glucose, when delivered orally as opposed to intravenously (Perley et al. 1967). Studies in experimental animals have demonstrated that GLP-1 and GIP are needed for the maintenance of normal glucose tolerance (Scrocchi et al. 1996; Miyawaki et al. 1999). GIP is released into the circulation after ingestion of a meal; fat and carbohydrates seem to be predominant stimulators, whereas protein seems to be less important. The GLP-1, on the other hand, is released into circulation minutes after meal ingestion; fat, carbohydrates, and protein seem all to be powerful stimulators of GLP-1 secretion. Both GIP and GLP-1 are rapidly inactivated after their release. The inactivation is caused by a truncation of the peptides by removal of the N-terminal dipeptide end; such a process is executed by the enzyme DPP-4. Inhibition of DPP-4 by gliptin class (vildagliptin, sitagliptin, saxagliptin) substantially prolongs this half-life and increases the proportion of active GLP-1 in the total GLp-1 pool. In patients with type 2 diabetes mellitus (T2DM), secretion of GLP-1 is lower than normal and increasing GLP-1 decreases blood glucose, which suggest that this hormone may contribute to the pathogenesis of T2DM. The major therapeutic drawback to using native GLP-1 is its very short half life of less than 2 (two) minutes following exogenous administration, due to in part to the protease DPP-4 (Deacon et al. 1995). There are 2 (two) approaches to enhance endogenous GLP-1 action in vivo Incretin Mimetic (GLP-1 Analogues and Exenatide = Exendin-4) and DPP-4 inhibitors (Vildagliptin, Sitagliptin, Saxagliptin) which may increase the incretin hormones (GLP-1 and GIP) by inhibiting the enzyme responsible for their degradation (Deacon et al. 1995). On the basis of the data on efficacy, safety, and tolerability of vildagliptin either in monotherapy or in combination, in patients failing monotherapy on other T2DM treatments, it can be concluded that vildagliptin 50 mg once daily and twice daily, and 100 mg once daily show: 1. promising regimen that can be used as a novel strategy for the treatment of T2DM; 2. therapeutic value if in combination with metformin, glitazone, and other commonly used OADs; 3. beneficial effects in diabetic insulin-treated patients with inadequate glycemic control.
Keyword :
Incretins, GIP, GLP-1, T2DM, Vidagliptin,
References :
Ahrén B, Landin-Olsson M, Jansson PA, et al.,(2004) Inhibition of dipeptidyl peptidase-IV reduces glycemia, sustained insulin levels, and reduces glucagons levels in type2 diabetes - : J Clin Endocrinol Metab
Barnett,(2006) DPP-4 inhibitors and their potential role in the management of type 2 diabetes - : Int J Clin Pract
Archive Article
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 Volume : 45 / No. : 3 / Pub. : 2009-07 |
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