GLP-1 Receptor Agonist Medications
GLP-1 receptor agonists include both short-acting agents (exenatide twice-daily, lixisenatide once-daily) and long-acting agents (liraglutide, exenatide once-weekly, dulaglutide, semaglutide, albiglutide), plus the dual GIP/GLP-1 receptor agonist tirzepatide. 1
Short-Acting GLP-1 Receptor Agonists
- Byetta (exenatide) - administered as a twice-daily subcutaneous injection for type 2 diabetes treatment 1
- Lyxumia (lixisenatide) - administered as a once-daily subcutaneous injection 1
- Exenatide was the first GLP-1 receptor agonist approved by the US Food and Drug Administration in 2005, sharing 50% homology with endogenous GLP-1 and demonstrating resistance to dipeptidyl peptidase-4 cleavage 2
Long-Acting GLP-1 Receptor Agonists
- Victoza (liraglutide) - used for both diabetes management and weight loss, with FDA approval for daily 3 mg dosing in patients with BMI >30 or >27 with comorbidities 2, 1
- Byetta (exenatide once-weekly) - long-acting formulation encapsulated in microspheres for extended release 2, 1
- Trulicity (dulaglutide) - modified through conjugation with the fragment crystallisable region of immunoglobulin G to prolong elimination 2, 1
- Ozempic/Wegovy (semaglutide) - a liraglutide analogue with greater albumin affinity, approved as weekly 2.4 mg dosing for weight loss in 2021 2, 1, 3
- Eperzan (albiglutide) - achieves prolonged action through non-covalent conjugation with albumin 2, 1
Dual GIP/GLP-1 Receptor Agonist
- Mounjaro (tirzepatide) - activates both GIP and GLP-1 receptors, demonstrating superior efficacy with greater reductions in HbA1c and body weight compared to selective GLP-1 receptor agonists like semaglutide and dulaglutide 2, 4, 1
- Tirzepatide binds to the GIP receptor but has approximately five times less affinity for the GLP-1 receptor compared to endogenous GLP-1 2, 4
- At higher doses (15 mg), tirzepatide achieved mean weight loss of 20.9% at 72 weeks in non-diabetic obese patients 2
Mechanism Distinguishing Short vs. Long-Acting Agents
- All GLP-1 receptor agonists have been molecularly modified to prevent rapid cleavage and inactivation by dipeptidyl peptidase-4 2
- Short-acting agents like exenatide require at least once-daily administration 2
- Long-acting agents achieve extended elimination half-lives through various molecular modifications including albumin binding (semaglutide, albiglutide), immunoglobulin conjugation (dulaglutide), or microsphere encapsulation (long-acting exenatide) 2