Lixisenatide, a Once-Daily Prandial Glucagon-Like Peptide-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes.

Abstract

Lixisenatide, a short-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), has been available in Europe since 2013 and was recently approved in the United States for the treatment of type 2 diabetes (T2D) as an adjunct to diet and exercise. The objective of this systematic review is to describe the pharmacology, pharmacokinetics, safety, and efficacy of lixisenatide in patients with T2D. We conducted a search of the EMBASE database, limited to human studies with abstracts available in English. Published conference abstracts, limited to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes meetings in 2015, as well as abstracts presented at the ADA meeting in 2016, were also screened. The abstracts retrieved were assessed for relevance; review articles and meta-analyses focusing on GLP-1 RAs as a class were excluded. Lixisenatide induced mean reductions of 0.46-0.99% in glycated hemoglobin A1c (HbA1c ), 55.86-143.43mg/dl in 2-hour postprandial glucose (PPG) levels, and 56.58-127.75mg/dl in mealtime glucose level variations. Changes in fasting plasma glucose (FPG) levels and weight ranged from -21.98 to +5.41mg/dl and from -2.96 to +0.3kg, respectively, in patients with T2D enrolled in the GetGoal clinical program (a program of clinical trials that established the efficacy and safety profile of lixisenatide 20μg once/day across patients with T2D with differing background therapies). Lixisenatide was well tolerated, demonstrating rates of symptomatic hypoglycemia of 0.8-42.9% and a very low rate of severe hypoglycemia (<1.5%) as well as no increased risk of cardiovascular events. The most common adverse events were gastrointestinal in nature, mainly transient nausea and vomiting of mild-to-moderate severity. Lixisenatide effectively lowers HbA1c levels in patients with T2D through a mechanism of action complementary to that of agents that mainly target FPG, with the additional benefit of weight loss. Its once-daily administration schedule and effect on PPG levels make it an attractive option as add-on treatment to basal insulin therapy or oral antidiabetic agents.