Review of the therapeutic uses of liraglutide

Glucagon-like peptide (GLP-1) is a neuroendocrine hormone that increases blood glucose and is a drug target for treatment of type 2 diabetes. Liraglutide, a subcutaneous, once-daily GLP-1 agonist, is approved for the treatment of type 2 diabetes in the United States and Europe. It also has been studied for weight loss.

The purpose of this article is to review all of the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions, cost, and place in therapy of liraglutide.

Literature searches of MEDLINE between 1969 and September 2010, International Pharmaceutical Abstracts between 1970 and September 2010, American Diabetes Association Meeting abstracts (2008-2010), and European Association for the Study of Diabetes abstracts (2008-2010) were performed using liraglutide, Victoza, and NN2211 as key terms.

Thirteen randomized controlled trials were identified and summarized. Liraglutide has been shown to increase glucose-dependent insulin release by 34% to 118% and reduce postprandial glucagon levels by 20%. Studies showed that liraglutide, as monotherapy and in combination with glimepiride, metformin, and/or rosiglitazone, lowers glycosylated hemoglobin (HbA(1c)) between 0.84% and 1.5%. Transient nausea was reported by 7% to 40% of subjects. Severe hypoglycemia-glucose <55 mg/dL-was observed by 2.5% of subjects in 1 trial.

Liraglutide safely and effectively reduces HbA(1c) in patients with type 2 diabetes. The most recent American Diabetes Association guidelines recommended a GLP-1 agonist along with metformin as a second-tier therapy for type 2 diabetes. Although the American Association of Clinical Endocrinologists/American College of Endocrinologists' guidelines recommended it for first-line monotherapy in patients with HbA(1c) between 6.5% and 7.5% and with metformin if HbA(1c) is between 7.6% and 8.5%, liraglutide should be considered for patients who cannot tolerate first-line agents or if an additional agent is needed to help reach target HbA(1c) goals.