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NEW DRUG DEVELOPMENTS

Liraglutide: A Once-Daily Incretin Mimetic for the Treatment of Type 2 Diabetes Mellitus

Assistant Professor, Department of Pharmacotherapy, College of Pharmacy, Washington State University/Elder Services, Spokane, WA

R Keith Campbell, BSPharm MBA CDE FASHP FAPhA

Distinguished Professor in Diabetes Care, Department of Pharmacotherapy, College of Pharmacy, Washington State University, Pullman, WA

Reprints: Dr. Neumiller, Department of Pharmacotherapy, College of Pharmacy, Washington State University/Elder Services, 5125 N. Market St., Spokane, WA 99217, fax 509/458-7459, jneumiller{at}wsu.edu

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of liraglutide, a glucagon-like peptide 1 (GLP-1) analog for the treatment of type 2 diabetes mellitus.

DATA SOURCES: A MEDLINE search (1966-May 2009) was conducted for English-language articles using the terms glucagon-like peptide 1, incretin mimetic, NN2211, and liraglutide. Abstracts presented at the American Diabetes Association and European Association for the Study of Diabetes annual meetings in 2006, 2007, and 2008 were also searched for relevant data.

STUDY SELECTION AND DATA EXTRACTION: Articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of liraglutide were reviewed.

DATA SYNTHESIS: Liraglutide is a GLP-1 analog with pharmacokinetic properties suitable for once-daily administration. Clinical trial data from large, controlled studies demonstrate the effectiveness of liraglutide in terms of hemoglobin A_1c (A1C) reduction, reductions in body weight, and the drug's low risk for hypoglycemic events when used as monotherapy. Data also support benefits of liraglutide therapy on β-cell responsiveness to glucose, with animal and in vitro data indicating potential benefits in β-cell mass and neogenesis with liraglutide treatment. Liraglutide has been studied as monotherapy and in combination with metformin, glimepiride, and rosiglitazone for the treatment of type 2 diabetes. Additionally, comparative data with insulin glargine and exenatide therapy are available from Phase 3 trials providing practitioners valuable clinical data on which to base clinical decision making. Overall, liraglutide is well tolerated with dose-dependent nausea, vomiting, and diarrhea being the most commonly reported adverse events in clinical trials.

CONCLUSIONS: Once-daily administration may provide a therapeutic advantage for liraglutide over twice-daily exenatide, with similar improvements in A1C and body weight observed when liraglutide was compared with exenatide. The glucose-dependent mechanism of insulin release with GLP-1 agonist therapy holds potential clinical significance in the management of postprandial hyperglycemic excursions, with minimal risk of hypoglycemia.

Key Words: glucagon-like peptide 1 analog, incretin mimetic, liraglutide, NN2211

Published Online, July 28, 2009. www.theannals.com, DOI 10.1345/aph.1M134

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-09-017-H01-P