What do I need to know about liraglutide (Saxenda), the glucagon-like peptide 1 receptor agonist for weight management in children with obesity?

Abstract

Glucagon-like peptide 1 (GLP-1) is a gut hormone, or incretin, which is secreted into circulation by intestinal L cells in response to nutritional intake (1). Although incretin-based therapies, such as GLP-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase 4 inhibitors (DPP-4i), are now well established as effective agents in the control of type 2 diabetes (T2D) and obesity in adults (2), their application in children is relatively novel. In early 2021, Health Canada approved a once daily subcutaneous injectable formulation of the GLP-1RA liraglutide (Saxenda) for use as a weight management therapy in adolescents with obesity (3). The same drug given at a lower dose of 1.8 mg daily (Victoza) was approved in 2020 for use as an add on therapy to metformin in children and adolescents with T2D (4). Once in circulation, GLP-1 acts by increasing insulin secretion and sensitivity, inhibiting glucagon secretion, slowing gastrointestinal motility, and inducing satiety through interaction with the central nervous system (5). Preloaded syringes of Saxenda deliver an adjustable dose of up to 3 mg of liraglutide (C172H265N43O51), a GLP-1 analogue with an amino acid substitution (arginine for lysine) and C-16 fatty acid addition. These alterations confer protection from its degrading exopeptidase counterpart, DPP-4, which typically limits the half-life of intrinsically produced GLP-1 to seconds or minutes in circulation (6). GLP-1RA are designed to mimic the effects of endogenous GLP-1 over a prolonged period, given their resistance to degradation.