GLP-1 Agonist

Tirzepatide is a synthetic 39-amino acid polypeptide conjugated with a C20 fatty diacid moiety that functions as the first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Approved by the FDA in May 2022 for type 2 diabetes (brand name Mounjaro) and November 2023 for chronic weight management (brand name Zepbound), it demonstrates superior glycemic control and weight reduction compared to selective GLP-1 agonists. Clinical trials show dose-dependent weight loss of 15-21% and HbA1c reductions up to 2.58% over 40-72 weeks. The compound exhibits biased agonism, with greater affinity for GIP receptors and preferential cAMP signaling at GLP-1 receptors, contributing to enhanced beta-cell function and insulin sensitivity. In gray market contexts, tirzepatide is sold as a research chemical with significant quality and safety concerns, as unapproved versions lack FDA oversight for purity, sterility, and accurate dosing.

Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist with 94% structural homology to human GLP-1, featuring three key modifications that provide enzymatic stability and extended half-life of approximately one week. Approved by the FDA in multiple formulations (Ozempic for diabetes, Wegovy for obesity, Rybelsus as oral formulation), it functions by enhancing glucose-dependent insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through central and peripheral mechanisms. Semaglutide has demonstrated significant cardiovascular benefits with 20-26% risk reduction in major adverse cardiac events, substantial weight loss outcomes (14-17% body weight reduction), and improvements in glycemic control with HbA1c reductions of 1.0-1.8%. Despite its FDA-approved status, semaglutide has entered gray markets as a research chemical sold without prescription, with quality testing revealing dramatically substandard purity levels (7-14% versus claimed 99%), endotoxin contamination, and significant safety concerns regarding compounded and unregulated sources.