Types of GLP-1 Receptor Agonists
FDA-Approved GLP-1 Receptor Agonists
There are currently five FDA-approved GLP-1 receptor agonists available in the United States, administered via subcutaneous injection at varying frequencies, plus one oral formulation. 1, 2
Once-Weekly Injectable Formulations
Semaglutide (Ozempic/Wegovy): Available as 0.25-2.4 mg weekly subcutaneous injection, with Ozempic approved for type 2 diabetes and Wegovy (2.4 mg) specifically approved for obesity management 1, 3
Dulaglutide (Trulicity): Administered as 0.75-4.5 mg once weekly subcutaneous injection, approved for type 2 diabetes in adults and pediatric patients ≥10 years old 1, 4
Exenatide extended-release (Bydureon): Given as 2 mg once weekly subcutaneous injection 1
Albiglutide (Eperzan): Dosed at 30-50 mg once weekly, though availability may be limited 1
Once-Daily Injectable Formulations
Liraglutide (Victoza/Saxenda): Available as 0.6-3.0 mg daily subcutaneous injection, with Victoza approved for diabetes and Saxenda (3.0 mg) approved for obesity management 1
Lixisenatide (Lyxumia): Administered as 10-20 mcg once daily subcutaneous injection 1
Twice-Daily Injectable Formulation
- Exenatide immediate-release (Byetta): Given as 5-10 mcg twice daily subcutaneous injection 1
Oral Formulation
- Oral semaglutide (Rybelsus): The only oral GLP-1 receptor agonist, though it has lower bioavailability (0.8%) compared to subcutaneous formulations (89%) and is FDA-approved only for type 2 diabetes, not obesity management 1, 5
Dual GIP/GLP-1 Receptor Agonist
Tirzepatide (Mounjaro/Zepbound) represents a distinct drug class as a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, not a pure GLP-1 agonist. 1, 5
- Administered as 5-15 mg once weekly subcutaneous injection 1
- FDA-approved in November 2023 for obesity treatment, demonstrating superior weight loss (20.9%) compared to semaglutide (14.9%) 5
- Classified separately by the American Diabetes Association as a "Dual GIP and GLP-1 RA" rather than a traditional GLP-1 receptor agonist 5
Key Pharmacokinetic Differences
Elimination Half-Life
- Long-acting agents (once-weekly): Semaglutide (7 days), dulaglutide (4.5-4.7 days), albiglutide (5 days), exenatide ER (2.4 hours but sustained release) 1
- Short-acting agents (daily/twice-daily): Liraglutide (13 hours), lixisenatide (3 hours), exenatide IR (2.4 hours) 1
Renal Dosing Considerations
- No dose adjustment required: Semaglutide, liraglutide, dulaglutide across all stages of chronic kidney disease 1, 5
- Caution or not recommended: Exenatide formulations and lixisenatide require dose adjustments or avoidance in moderate-to-severe renal impairment 1
Clinical Selection Considerations
For obesity management in adults, prioritize semaglutide 2.4 mg weekly or tirzepatide 15 mg weekly based on the magnitude of weight loss needed and cardiovascular risk profile. 1, 5
- Tirzepatide achieves greatest weight loss (20.9% at 72 weeks) but lacks long-term cardiovascular outcome data 5
- Semaglutide 2.4 mg produces 14.9% weight loss with proven cardiovascular benefit (20% reduction in MACE) in patients with established cardiovascular disease 1, 5
- Liraglutide 3.0 mg achieves more modest weight loss (5.2-6.1%) but may be preferred when weekly injections are not tolerated 1, 5
For type 2 diabetes with obesity, tirzepatide demonstrates superior efficacy for both glycemic control and weight loss compared to all GLP-1 receptor agonists. 1, 5