Liraglutide — GLP-1 receptor agonist (daily injection)

Liraglutide produces ~6-8% weight loss from baseline (Saxenda), compared to ~15% for semaglutide 2.4mg (Wegovy) and ~22% for tirzepatide 15mg. The lower efficacy is partly due to daily vs weekly dosing (less sustained receptor activation) and absence of GIP agonism. LEADER trial (2016) was the first GLP-1 trial to demonstrate CV mortality reduction, establishing the cardiovascular rationale for the entire drug class. Discontinuation rates are higher than semaglutide due to frequent daily injections.

Overview

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Compound Class

GLP-1 receptor agonist (daily injection)

Mechanism of Action

Liraglutide is a fatty-acid acylated GLP-1 analog with 97% sequence homology to native GLP-1. The C-16 fatty acid chain enables albumin binding, extending half-life from ~2 minutes (native GLP-1) to ~13 hours, enabling once-daily dosing. Activates GLP-1 receptors in pancreatic β-cells (glucose-dependent insulin secretion), hypothalamic appetite centers (reduces energy intake ~500 kcal/day), brainstem (nausea/satiety signaling), and GI tract (slows gastric emptying). Cardioprotective mechanism: anti-inflammatory effects on coronary vasculature, reduced platelet aggregation, and direct GLP-1 receptor effects in cardiomyocytes — demonstrated in LEADER trial (13% MACE reduction). Predates semaglutide; used to establish GLP-1 agonist cardiovascular safety profile.

Regulatory Status

FDA approved — Victoza (T2DM, 2010), Saxenda (obesity, 2014)

Evidence Level

High — SCALE Phase 3 program (weight), LEADER trial (cardiovascular outcomes in T2DM)