NEUROENDOCRINE ASSOCIATION OF TIRZEPATIDE: IMPLICATIONS FOR ENERGY HOMEOSTASIS AND HYPOTHALAMIC REGULATION

Abstract

Tirzepatide represents a significant pharmacological advance in the treatment of obesity and type 2 diabetes mellitus due to its dual action as an agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. In addition to the classic pancreatic effects related to insulin secretion and glycemic reduction, recent evidence demonstrates important central neuroendocrine activity, especially on hypothalamic circuits involved in energy homeostasis. This article reviews the neurobiological mechanisms associated with tirzepatide, emphasizing its interaction with the gut-brain axis, modulation of orexigenic and anorexigenic neurons, influence on hedonic dopaminergic pathways, and impact on systemic metabolic regulation. The role of the arcuate hypothalamus, paraventricular nucleus, and brainstem in mediating the anorexigenic and metabolic effects of the drug is also discussed. Although clinical results demonstrate greater weight loss than that observed with isolated GLP-1 agonists, gaps remain regarding the exact central mechanisms of GIP/GLP-1 coactivation. A deeper understanding of these pathways may broaden future therapeutic applications in metabolic and neuroendocrine diseases.