GLP-1 Receptor Agonist Examples
Semaglutide, liraglutide, dulaglutide, and tirzepatide are the primary GLP-1 receptor agonists used in clinical practice, with semaglutide and tirzepatide demonstrating superior efficacy for both weight loss and glycemic control. 1
FDA-Approved GLP-1 Receptor Agonists
Injectable Formulations
Liraglutide (Victoza, Saxenda): A once-daily subcutaneous GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1, approved for type 2 diabetes at doses up to 1.8 mg daily and for obesity management at 3.0 mg daily 2, 1
Semaglutide (Ozempic, Wegovy): Available as once-weekly subcutaneous injection, with 1.0 mg approved for type 2 diabetes and 2.4 mg approved for obesity management, achieving mean weight loss of 14.9% at 68 weeks 1, 3
Dulaglutide (Trulicity): A once-weekly subcutaneous injection containing a GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1, available in doses of 0.75 mg, 1.5 mg, 3 mg, and 4.5 mg 4, 1
Tirzepatide (Mounjaro, Zepbound): A dual GIP/GLP-1 receptor agonist administered once weekly, FDA-approved in 2023 for obesity, achieving superior weight loss of 20.9% at 72 weeks with the 15 mg dose 1, 5
Oral Formulation
- Oral semaglutide (Rybelsus): FDA-approved only for type 2 diabetes treatment, not for obesity management, and demonstrates less potent weight loss effects compared to injectable formulations 1, 3
Mechanism of Action Shared Across GLP-1 Receptor Agonists
All GLP-1 receptor agonists work through common pathways:
Glucose-dependent insulin secretion: They activate GLP-1 receptors on pancreatic beta cells, increasing intracellular cyclic AMP and leading to insulin release only in the presence of elevated glucose concentrations 2, 4
Glucagon suppression: They decrease glucagon secretion in a glucose-dependent manner, reducing hepatic glucose production at hyper- or euglycemia 2, 3
Delayed gastric emptying: They slow the rate at which nutrients enter circulation, prolonging satiety and reducing postprandial glucose excursions 2, 6
Central appetite suppression: They activate receptors in the hypothalamus and brainstem nuclei that mediate satiety, energy intake, and expenditure 6, 1
Comparative Efficacy
Tirzepatide demonstrates the greatest weight loss efficacy (20.9%), followed by semaglutide 2.4 mg (14.9%), then liraglutide 3.0 mg (5.24-6.1%). 1
For glycemic control in type 2 diabetes, tirzepatide produces greater HbA1c reductions compared to semaglutide and dulaglutide, with all agents effectively reducing HbA1c by 1.48-2.24% 1, 5
Dosing Distinctions
Short-Acting vs Long-Acting
Short-acting agents (exenatide twice daily, lixisenatide once daily): Have reduced effectiveness on overnight and fasting plasma glucose but maintain gastric emptying effects during long-term treatment 3
Long-acting agents (liraglutide, semaglutide, dulaglutide, tirzepatide): Have more profound effects on overnight and fasting plasma glucose, with gastric emptying effects that may diminish over time due to tachyphylaxis 3, 6
Common Pitfalls
The most critical distinction is that oral semaglutide is NOT approved for obesity management and should not be confused with injectable semaglutide 2.4 mg (Wegovy) when prescribing for weight loss. 1 Additionally, clinicians must recognize that tirzepatide's dual receptor mechanism (GIP/GLP-1) makes it technically distinct from pure GLP-1 receptor agonists, though it shares similar clinical effects and is often grouped with this class. 5