Liraglutide: A once-daily human glucagon-like peptide-1 analogue for type 2 diabetes mellitus

Abstract

The pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, adverse effects, and place in therapy of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, are reviewed. Liraglutide, the first once-daily human GLP-1 analogue, retains 97% homology with the endogenous hormone and shares its glucose-dependent glucose-lowering action but has a considerably longer half-life that supports once-daily dosing. After promising Phase II study results, the Liraglutide Effect and Action in Diabetes (LEAD) Phase III clinical development program, involving more than 4000 patients worldwide, investigated the efficacy and tolerability of liraglutide 1.2 or 1.8 mg daily (n = 2735) as monotherapy and in combination with various oral antidiabetic drugs. The LEAD studies yielded encouraging results indicating that patients receiving liraglutide could expect to attain glycosylated hemoglobin reductions of about 1-1.5% and fasting plasma glucose reductions of 15-43 mg/dL. Loss of body weight was consistent throughout the studies: when using liraglutide 1.8 mg as monotherapy, patients lost a mean of 2.5 kg over a 52-week period. Accompanying reductions in some cardiovascular risk endpoints, such as systolic blood pressure, were also observed. By virtue of its glucose-dependent mode of action, liraglutide was generally well tolerated in clinical trials, with only very rare episodes of major hypoglycemia reported. The most frequently observed adverse effects were gastrointestinal, with 10-40% of patients experiencing an episode of nausea, which was often mild or moderate in severity and transient in nature. Liraglutide is efficacious and well tolerated in patients with type 2 diabetes and has been found to reduce weight and blood pressure.