Indications
Liraglutide is available in two primary formulations: Saxenda and Victoza. Saxenda is prescribed as a supplementary treatment to diet and exercise for long-term weight management in adults with a body mass index (BMI) of 30 kg/m² or higher, or for those with a BMI of 27 kg/m² or higher who also have at least one weight-related comorbidity. Additionally, it is indicated for use in pediatric patients aged 12 years and older, weighing at least 60 kg, whose BMI meets the international criteria for obesity. Victoza, on the other hand, is indicated for improving glycemic control in patients aged 10 years and older with type 2 diabetes mellitus, in conjunction with diet and exercise. Moreover, it is indicated to reduce the risk of major adverse cardiovascular events in adult patients with type 2 diabetes and established cardiovascular disease. Liraglutide is also available combined with insulin degludec to enhance glycemic control in adults with type 2 diabetes mellitus.
Pharmacodynamics
Liraglutide functions as a once-daily GLP-1 analog, specifically engineered for managing type 2 diabetes. Its extended duration of action is attributed to the addition of a fatty acid molecule at position 26 of the GLP-1 structure, allowing it to bind reversibly to albumin in both subcutaneous tissue and the bloodstream. This binding leads to a gradual release over time, preventing rapid degradation and enhancing its circulation longevity compared to native GLP-1. Liraglutide increases insulin secretion and reduces glucagon release in response to elevated glucose levels, while also delaying gastric emptying. Importantly, it does not affect glucagon secretion during episodes of hypoglycemia.
Absorption
Upon subcutaneous administration, liraglutide demonstrates a bioavailability of approximately 55%. Peak plasma concentrations are typically achieved around 11.7 hours post-injection.
Metabolism
Liraglutide displays greater resistance to metabolic breakdown than endogenous GLP-1, leading to slower degradation by enzymes such as dipeptidyl peptidase-4 and neutral endopeptidase. This results in the formation of several smaller polypeptides, not all of which have been structurally characterized. A fraction of liraglutide undergoes complete metabolism to carbon dioxide and water.
Mechanism of Action
Liraglutide is an acylated synthetic analog of glucagon-like peptide-1, functioning as an agonist of the glucagon-like peptide-1 receptor, which is linked to adenylate cyclase. This interaction results in an elevation of cyclic AMP, which, in turn, stimulates the glucose-dependent release of insulin and curtails the glucose-dependent release of glucagon. Additionally, Liraglutide decelerates gastric emptying, thereby enhancing the management of blood glucose levels.
