Extension of the group of incretin-targeted preparations: Saxagliptin

Shestakova M.V.

Institut diabeta Éndokrinologicheskogo nauchnogo tsentra, Moskva

Sukhareva O.Iu.

Institut diabeta Éndokrinologicheskogo nauchnogo tsentra, Moskva

Extension of the group of incretin-targeted preparations: Saxagliptin – a new dipeptidyl peptidase-4 inhibitor

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Shestakova M.V., Sukhareva O.Iu.

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Journal: Problems of Endocrinology. 2010;56(5): 52‑60

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Shestakova MV, Sukhareva OIu. Extension of the group of incretin-targeted preparations: Saxagliptin – a new dipeptidyl peptidase-4 inhibitor. Problems of Endocrinology. 2010;56(5):52‑60. (In Russ.)

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A new selective incretin-targeted dipeptidyl peptidase-4 inhibitor was registered in the Russian Federation in August 2010. The enzyme dipeptidyl peptidase-4 inactivates glucagon-like peptide-1 (GLP-1). A rise of GLP-1 concentration in blood plasma is known to result in the glucose-dependent stimulation of insulin secretion by pancreatic beta-cells and suppression of glucagon release. Saxagliptin is readily absorbed in the gastrointestinal tract and remains active within 24 hours after oral intake. It allows the drug to be taken once during 24 hours. Clinical studies have demonstrated that saxagliptin improves glycemic control when used as both monotherapy and in combination with other antidiabetic medicines (metformin, sulfonylureas, and thiazolidinediones). The use of saxagliptin leads to a reduction of fasting and postprandial plasma glucose level and thereby to the clinically significant decrease in glycated hemoglobin (HbA1c) concentration. The low risk of hypoglycemia following saxagliptin intake is due to the glucose-dependent mechanism of its action. The results of clinical investigations indicate that saxagliptin is safe and well tolerated by the patients and has no significant influence on their body weight; its dose does not need to be corrected for the sex and age of the patients or the presence of concomitant hepatic disorders.

Keywords:

dipeptidyl peptidase-4 inhibitors

glucagon-like peptide-1

glycemic control

saxagliptin

type 2 diabetes mellitus

Authors:

Shestakova M.V.

Institut diabeta Éndokrinologicheskogo nauchnogo tsentra, Moskva

Sukhareva O.Iu.

Institut diabeta Éndokrinologicheskogo nauchnogo tsentra, Moskva

List of references:

Deacon C.F., Carr R.D., Holst J.J. DPP-4 inhibitor therapy: new directions in the treatment of type 2 diabetes. Front Biosci 2008;13:1780-1794.
Baggio L.L., Drucker D.J. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-2157.
Holst J.J. The physiology of glucagon-like peptide 1. Physiol Rev 2007;87:1409-1439.
Holst J.J., Vilsboll T., Deacon C.F. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 2009;297:127-136.
Vilsboll T., Holst J.J. Incretins, insulin secretion and type 2 diabetes mellitus. Diabetologia 2004;47:357-366.
Nauck M.A., Kleine N., Orskov C. et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993;36:741-744.
Rachman J., Barrow B.A., Levy J.C., Turner R.C. Near-normalisation of diurnal glucose concentrations by continuous administration of glucagon-like pep-tide-1 (GLP-1) in subjects with NIDDM. Diabetologia 1997;40:205-211.
Zander M., Madsbad S., Madsen J.L., Holst J.J. Effect of 6-week course of glucagon-like peptide 1 on gly-caemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824-830.
Deacon C.F., Nauck M.A., Toft-Nielsen M. et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995;44:1126-1131.
Augeri D.J., Robl J.A., Betebenner D.A. et al. Discovery and preclinical profile of saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipepti-dyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005;48:5025-5037.
Henry R., Smith S., Schwartz S. et al. p-Cell stimulation by saxagliptin in patients with T2D [abstract no. 447-P plus poster]. 69th Annual Scientific Sessions of the American Diabetes Association. New Orleans 2009.
Boulton D.W., Geraldes M. Safety, tolerabilty, pharmacokinetics and pharmacodynamics of once-daily oral doses of saxagliptin for 2 weeks in type 2 diabetic and healthy subjects [abstract no. 606-P plus poster]. 67th Scientific Sessions of the American Diabetes Association. Chicago 2007.
Kirby M.S., Dorso C., Wang A. et al. In vitro enzy-mologic characteristics of saxagliptin, a highly potent and selective DPP4 inhibitor with "slow binding" characteristic [abstract]. Clin Chem Lab Med 2008;46:A29.
Patel C.G., Li L., Komoroski B.J. et al. No effect ofsaxagliptin on QTc interval in healthy subjects [abstract no. 2072-PO]. 69th Annual Scientific Sessions of the American Diabetes Association. New Orleans 2009.
Fura A., Khanna A., Vyas V. et al. Pharmacokinetics of the dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and monkeys and clinical projections. Drug Metab Dis 2009;37:6:1164-1171.
Boulton D., Tang A., Patel C. et al. Pharmacokinetics of dipeptidyl pepetidase-4 inhibitor saxagliptin in subjects with renal impairment [abstract no. P357]. 11th European Congress of Endocrinology. Istanbul 2009.
Patel C., Castaneda L., Frevert U. et al. Single-dose pharmacokinetics and safety of saxagliptin in subjects with hepatic impairment compared with healthy subjects [abstract no. 537-P]. Diabetes 2008;57:Suppl 1:A160.
Rosenstock J., Sankoh S., List J.F. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 2008;10:5:376-386.
Rosenstock J., Aguilar-Salinas C., Klein E. et al. Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin 2009;25:10:2401-2411.
DeFronzo R.A., Hissa M.N., Garber A.J. et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes on metformin alone. Diabet Care 2009;32:9:1649-1655.
Defronzo R.A., Hissa M.N., Garber A.J. et al. Once-daily saxagliptin added to metformin provides sustained glycaemic control and is well tolerated over 102 weeks in patients with T2D [abstract no. 547-P]. 69th Annual Scientific Sessions ofthe American Diabetes Association. New Orleans 2009.
Jadzinsky M., Pfutzner A., Paz-Pacheco E. et al. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009;11:6:611-622.
Chacra A.R., Tan G.H., Apanovitch A. et al. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonyl-urea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 2009;63:9:1395-1406.
Hollander P., Allen E., Li J., Chen R. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with inadequately controlled type 2 diabetes [abstract]. Diabetologia 2008;51: Suppl 1:S342.
Wolf R., Frederich R., Fiedorek F. et al. Evaluation of CV risk in saxagliptin clinical trials [abstract no. 8-LB plus poster]. 69th Annual Scientific Sessions of the American Diabetes Association. New Orleans 2009.

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