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NEW DRUG DEVELOPMENTS

Incretin Mimetics as Emerging Treatments for Type 2 Diabetes

Assistant Professor of Clinical Medicine, Duke University Medical Center, Durham, NC

Philip T Rodgers, PharmD BCPS CDE CPP

Clinical Assistant Professor, University of North Carolina; Clinical Pharmacist, Duke University Health System

Ann C Scates, PharmD

Clinical Pharmacist and Drug Information Specialist, Duke University Hospital

Reprints: Dr. Joy, Duke University Medical Center, 3024 Pickett Rd., Durham, NC 27705-0493, fax 919/419-5842, joy00002{at}mc.duke.edu

OBJECTIVE: To review the physiology, pharmacology, and clinical efficacy of glucagon-like peptide (GLP-1) and the incretin mimetics exenatide and liraglutide in clinical studies.

DATA SOURCES: Primary literature obtained via MEDLINE (1966–April 2004) and International Pharmaceutical Abstracts (1970–April 2004) searches; abstracts obtained from meeting sources and manufacturers.

STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts evaluating GLP-1, exenatide, and liraglutide in the treatment of patients with type 2 diabetes were reviewed. Data from animal studies were also included if human data were not available. Primary and review articles related to the physiology, development, and evaluation of GLP-1s were reviewed.

DATA SYNTHESIS: GLP-1, exenatide (exendin-4, AC2993), and liraglutide (NN2211) are incretin mimetics that have been shown in human studies to be an effective treatment to improve glycemic control in patients with type 2 diabetes. Mechanisms by which these compounds improve glycemic control include enhancing glucose-dependent pancreatic secretion of insulin in response to nutrient intake, inhibiting glucagon secretion, delaying gastric emptying, and promoting early satiety. GLP-1 has been shown to promote pancreatic progenitor cell differentiation and improve ß-cell function and lifespan. Reported adverse effects of exenatide and liraglutide include nausea, vomiting, and transient headache, as well as increased risk of hypoglycemia when used with sulfonylureas.

CONCLUSIONS: Clinical studies show that GLP-1, exenatide, and liraglutide improve glycemic control for patients with type 2 diabetes through unique mechanisms not available with current pharmaceutical products. Ongoing Phase III studies will help to further position these compounds as treatment options for patients with type 2 diabetes.

Key Words: exenatide, glucagon-like peptides, incretin mimetics, liraglutide, type 2 diabetes

Published Online, November 23, 2004. www.theannals.com, DOI 10.1345/aph.1E245

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