What is the Origin of GLP-1 Agonism?

The concept originated from the discovery of GLP-1, an incretin hormone released by L-cells in the intestine in response to nutrient ingestion. Scientists subsequently developed synthetic peptide analogs that mimic the action of native GLP-1 but possess a much longer half-life, leading to the clinical application of GLP-1 receptor agonists. This represents a significant advance in metabolic endocrinology.

What is the Mechanism of GLP-1 Agonism?

Activation of the GLP-1 receptor on pancreatic beta cells increases intracellular cyclic AMP (cAMP), potentiating the release of insulin in a glucose-dependent manner, thereby lowering blood sugar without a high risk of hypoglycemia. Simultaneously, GLP-1 signaling in the brain's appetite centers, particularly the hypothalamus, reduces food intake and body weight. The overall effect is a multifaceted improvement in metabolic efficiency and energy homeostasis.

GLP-1 Agonism

Meaning

The pharmacological action of a substance that binds to and activates the Glucagon-like Peptide-1 (GLP-1) receptor, a G-protein coupled receptor expressed in pancreatic beta cells, the brain, and the gastrointestinal tract. This agonism enhances glucose-dependent insulin secretion, slows gastric emptying, and promotes satiety in the central nervous system. It is a key therapeutic strategy for managing type 2 diabetes and obesity.