Examples of GLP-1 Receptor Agonists
The currently available GLP-1 receptor agonists include exenatide (short- and long-acting formulations), liraglutide, lixisenatide, dulaglutide, albiglutide, semaglutide, and beinaglutide, with tirzepatide representing a newer dual GIP/GLP-1 receptor agonist. 1
Short-Acting GLP-1 Receptor Agonists
These agents require more frequent dosing but maintain stronger effects on gastric emptying:
- Exenatide (twice daily): The first FDA-approved GLP-1 receptor agonist in 2005, sharing 50% homology with endogenous GLP-1 and resistant to dipeptidyl peptidase-4 cleavage 1
- Lixisenatide (once daily): A short-acting agent that delays gastric emptying and has greater effects on postprandial glucose levels 1, 2
Long-Acting GLP-1 Receptor Agonists
These formulations allow for less frequent administration through molecular modifications that prolong elimination:
- Liraglutide (once daily): FDA-approved in 2010, modified with greater albumin affinity for prolonged action; available in 3 mg dose for weight loss (approved 2014) 1, 3
- Exenatide extended-release (once weekly): Drug encapsulated in microspheres that gradually release from a subcutaneous depot 1
- Dulaglutide (once weekly): Conjugated with the fragment crystallisable region of immunoglobulin G for prolonged elimination 1
- Albiglutide (once weekly): Non-covalently conjugated with albumin for extended duration 1
- Semaglutide (once weekly): A liraglutide analogue with greater albumin affinity; FDA-approved at 2.4 mg weekly for weight loss in 2021 1
- Beinaglutide: Available in China, requires subcutaneous injection 1
Dual GIP/GLP-1 Receptor Agonist
- Tirzepatide (once weekly): Binds to both GIP and GLP-1 receptors (with approximately five times less affinity for GLP-1 receptor than endogenous GLP-1), producing greater reductions in HbA1c and body weight compared to semaglutide and dulaglutide 1
Key Distinguishing Features
Dosing frequency separates these agents into practical categories: short-acting agents (exenatide twice daily, lixisenatide once daily) versus long-acting agents (all weekly formulations plus liraglutide once daily) 4, 2
Efficacy differences exist among agents: Liraglutide demonstrates greater HbA1c reductions compared to exenatide formulations and albiglutide, while long-acting agents show superior glycemic control compared to exenatide twice daily 2
Gastric emptying effects vary by duration of action: Short-acting agents maintain stronger effects on delaying gastric emptying due to less tachyphylaxis development, while long-acting agents show diminished gastric emptying effects with continuous exposure 1, 5