Semaglutide

Semaglutide is a synthetic analogue of glucagon-like peptide-1 (GLP-1) with 94% sequence homology to native GLP-1. It binds and activates GLP-1 receptors in the pancreas, hypothalamus, and peripheral tissues, driving glucose-dependent insulin secretion, glucagon suppression, slowed gastric emptying, and central appetite reduction via hypothalamic signaling. The C18 fatty diacid side chain enables albumin binding, extending plasma half-life to approximately 7 days — enabling once-weekly dosing protocols in research settings.

STEP trials (2021): Pivotal Phase 3 trials demonstrated 14.9% mean weight loss at 2.4 mg weekly over 68 weeks in non-diabetic obesity subjects.

SUSTAIN program: Multiple trials showing significant HbA1c reductions across Type 2 DM populations.

Cardiovascular: 26% relative risk reduction in major adverse cardiovascular events (MACE) compared to placebo.

NASH research: Emerging preclinical and early clinical data suggest hepatic fat reduction.

Neuroprotection: GLP-1 receptor signaling being studied in Alzheimer's and Parkinson's disease models.