Examples of GLP-1 Receptor Agonists
GLP-1 receptor agonists (GLP-1 RAs) are a class of injectable and oral medications used to treat type 2 diabetes and obesity, with examples including liraglutide (Victoza), semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide (Trulicity), exenatide (Byetta, Bydureon), lixisenatide, and albiglutide. 1, 2, 3
Available GLP-1 Receptor Agonists by Administration Frequency
Short-Acting Agents (Twice Daily or Once Daily)
- Exenatide (Byetta): 10 μg twice daily, requires dose adjustment with creatinine clearance >30 ml/min 1, 3
- Lixisenatide: 10 μg and 20 μg once daily, not recommended with eGFR <15 ml/min per 1.73 m² 1, 3
- Liraglutide (Victoza): 1.2 mg and 1.8 mg once daily for diabetes; 3.0 mg daily (Saxenda) for weight management, no dosage adjustment required for CKD 1, 2, 3
Long-Acting Agents (Once Weekly)
- Semaglutide (Ozempic): 0.5 mg and 1 mg once weekly for diabetes, no dosage adjustment required for CKD 1, 4, 3
- Semaglutide (Wegovy): 2.4 mg once weekly for obesity management, with proven cardiovascular benefits 2, 4
- Dulaglutide (Trulicity): 0.75 mg and 1.5 mg once weekly, no dosage adjustment required, can be used with eGFR >15 ml/min per 1.73 m² 1, 5, 3
- Exenatide extended-release (Bydureon): 2 mg once weekly, use with eGFR >45 ml/min per 1.73 m² 1, 3
- Albiglutide: Once weekly administration (note: withdrawn from market in some regions) 3
Oral Formulation
Dual GIP/GLP-1 Receptor Agonist
- Tirzepatide (Mounjaro, Zepbound): 5 mg, 10 mg, or 15 mg once weekly, represents a distinct drug class with dual receptor activation, no dosage adjustment required across all CKD stages 1, 2
Key Clinical Distinctions
Agents with Proven Cardiovascular Benefits
The choice of GLP-1 RA should prioritize agents with documented cardiovascular benefits, particularly in patients with established atherosclerotic cardiovascular disease. 1, 5, 8
- Liraglutide: 26% reduction in composite cardiovascular outcomes (HR 0.74,95% CI 0.58-0.95) 2, 8
- Semaglutide (injectable): 26% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.74,95% CI 0.58-0.95) 2, 5, 4
- Semaglutide 2.4 mg (Wegovy): 20% reduction in cardiovascular events (HR 0.80) in patients with obesity and established CVD 2, 5
- Dulaglutide: FDA-approved to reduce cardiovascular death, non-fatal MI, or non-fatal stroke in adults with T2D and established CVD 5, 8
Weight Loss Efficacy Comparison
- Tirzepatide 15 mg: Achieves 20.9% weight loss at 72 weeks, the most effective option currently available 2
- Semaglutide 2.4 mg: Achieves 14.9% weight loss at 68 weeks 2
- Liraglutide 3.0 mg: Achieves 5.24-6.1% weight loss 2
- Oral semaglutide: Less potent for weight management compared to injectable formulations 2, 7
Dosing Considerations for Chronic Kidney Disease
No dose adjustment is required for dulaglutide, liraglutide, or semaglutide across all stages of CKD, including eGFR <30 mL/min/1.73 m², making them preferred agents for long-term use in patients with renal impairment. 1, 8
- Exenatide requires caution with CrCl >30 ml/min 1
- Exenatide extended-release should be avoided with eGFR <45 ml/min per 1.73 m² 1
- Lixisenatide is not recommended with eGFR <15 ml/min per 1.73 m² 1
Common Pitfalls to Avoid
- Do not combine GLP-1 RAs with DPP-4 inhibitors, as they share overlapping mechanisms and provide no additional benefit 1
- Reduce sulfonylurea or insulin doses when initiating GLP-1 RAs to prevent hypoglycemia 1, 5
- Start with low doses and titrate slowly to minimize gastrointestinal side effects (nausea, vomiting, diarrhea) 1, 2
- Discontinue GLP-1 RAs at least 3 weeks before elective surgery (for semaglutide/tirzepatide) due to delayed gastric emptying and aspiration risk 2