This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Schnabel, C. A Search for Related Content Social Bookmarking                         What's this?

The incretin mimetic, exenatide: a novel treatment option for type 2 diabetes

Pharmaceuticals, Inc., 9360 Towne Centre Dr., Suite 110, San Diego, CA 92121, USA, catherine.schnabel{at}amylin.com

Exenatide, (BYETTA ^TM), is the first in a new class of agents termed incretin mimetics, which replicate several glucoregulatory effects of the endogenous incretin hormone, glucagon-like peptide-1 (GLP-1). Currently approved (April 2005) in the United States as an injectable adjunct to metformin and/or sulphonylurea therapy, exenatide improves glycaemic control through multiple mechanisms of action including: enhancement of glucose-dependent insulin secretion, restoration of first-phase insulin response, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying and reduction in food intake. Subcutaneous exenatide injected twice-daily before morning and evening meals shows immediate and sustained effects on both postprandial and fasting glucose concentrations and is accompanied by reductions in body weight. Since the actions of exenatide on insulin and glucagon secretion are glucose dependent, the risk of hypoglycaemia is minimised except when exenatide is used in conjunction with agents that induce hypoglycaemia, such as sulphonylureas. Mild-to-moderate nausea is the most common side effect, which can be reduced with dose titration upon initiation of therapy. The incretin mimetic, exenatide, is a novel therapeutic option to improve glycaemic control with potential weight reduction in patients with type 2 diabetes suboptimally controlled with metformin or a sulphonylurea.

Key Words: exenatide • BYETTATM • incretin mimetic • type 2 diabetes.

References

• Aronoff SL, Berkowitz K., Schreiner B., Want L. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectrum 2004;17: 183-90.[Abstract/Free Full Text]
• Perley M., Kipnis DM Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967;46: 1954-62.[Web of Science][Medline] [Order article via Infotrieve]
• Creutzfeldt W. The incretin concept today. Diabetologia 1979;16:75-85.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Green BD, Irwin N., Gault VA, O'Harte FPM, Flatt PR Development and therapeutic potential of incretin hormone analogues for type 2 diabetes. Br J Diabetes Vac Dis 2005;5:134-40.
• Toft-Nielsen MB, Damholt MB, Madsbad S. et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717-23.[Abstract/Free Full Text]
• Zander M., Madsbad S., Madsen JL, Holst JJ Effect of 6-week course of glucagon-like peptide 1 on glycemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824-30.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Drucker DJ Minireview: the glucagon-like peptides. Endocrinology 2001;142:521-7.[Abstract/Free Full Text]
• Nielsen LL, Young AA, Parkes D. Pharmacology of exenatide (synthetic exendin-4): A potential therapeutic for improved glycemic control of type 2 diabetes. Reg Pept 2004;117:77-88.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kolterman OG, Kim DD, Shen L. et al. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Amer J Health-Sys Pharmacy 2005;62:173-81.
• Fineman MS, Shen LZ, Taylor K., Kim DD, Baron AD Effectiveness of progressive dose-escalation of exenatide (exendin-4) in reducing dose-limiting side-effects in subjects with type 2 diabetes. Diabetes/Metab Res Rev 2004;20:4W11-17.
• DeFronzo RA, Ratner RE, Han J., Kim DD, Fineman MS, Baron AD Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092-100.[Abstract/Free Full Text]
• Buse B., Henry RR, Han J. et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628-35.[Abstract/Free Full Text]
• Kendall DM, Riddle MC, Rosenstock J. et al. Effects of exenatide (exendin4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083-91.[Abstract/Free Full Text]
• BYETTA Prescribing information, www.byetta.com
• Kolterman OG, Buse JB, Fineman MS et al. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003;88:3082-9.[Abstract/Free Full Text]
• Fineman MS, Bicsak TA, Shen LZ et al. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 2003;26:2370-7.[Abstract/Free Full Text]
• Fehse F., Trautmann ME, Holst JJ et al. Effects of Exenatide on First and Second Phase Insulin Secretion in Response to Intravenous Glucose in Subjects with Type 2 Diabetes. Diabetes 2004;53:A82, 351-OR.
• Heine RJ, Van Gaal LF, Johns D., Mihm MJ, Widel MH, Brodows RG for the GWAA study group. Exenatide versus insulin glargine: an open-label randomized comparator trial. Ann Intern Med 2005;(in press).
• Blonde L., Han J., Mac S., Poon T., Taylor K., Kim D. Exenatide (Exendin-4) Reduced A1C and Weight Over 82 Weeks in Overweight Patients With Type 2 Diabetes. Diabetes 2005;54:A118, 477-P.
• Kendall DM, Kim D., Poon T., Han J., Schnabel C., Fineman M., Trautmann M., Maggs D. Improvements in Cardiovascular Risk Factors Accompanied Sustained Effects on Glycemia and Weight Reduction in Patients with Type 2 Diabetes Treated with Exenatide for 82 Wk. Diabetes 2005;54:A4-A5,16-OR.

The British Journal of Diabetes & Vascular Disease, Vol. 5, No. 4, 227-235 (2005)
DOI: 10.1177/14746514050050040801


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Day and C. J Bailey Review: Pharmacological approaches to reduce adiposity The British Journal of Diabetes & Vascular Disease, May 1, 2006; 6(3): 121 - 125. [Abstract] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Schnabel, C. A Search for Related Content Social Bookmarking                         What's this?