What is the recommended dosage for Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide (Ozempic) and liraglutide (Victoza), for patients requiring GLP-1 therapy?

Recommended Dosing for GLP-1 Receptor Agonists

For patients requiring GLP-1 therapy, the recommended dosage should follow a gradual titration schedule starting with the lowest available dose to minimize gastrointestinal side effects, with specific dosing depending on the specific GLP-1 agent used. 1

General Dosing Principles

• Start with the lowest available dose and gradually titrate up to minimize gastrointestinal side effects
• Most GLP-1 RAs require no dose adjustment for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²)
• Continue titration until target dose or maximum tolerated dose is reached

Specific Dosing Recommendations by Agent

Semaglutide (Subcutaneous)

• Initial dose: 0.25 mg once weekly for 4 weeks
• Titrate to 0.5 mg once weekly for at least 4 weeks
• May increase to maximum dose of 1 mg once weekly if needed 1
• No dose adjustment required for renal impairment down to eGFR of 15 mL/min/1.73 m² 1

Liraglutide (Victoza)

• Initial dose: 0.6 mg once daily for one week (to reduce GI side effects)
• Increase to 1.2 mg once daily after one week
• May increase to maximum dose of 1.8 mg once daily if needed after at least one week at 1.2 mg 2
• No dose adjustment required for renal impairment 1

Dulaglutide

• Initial dose: 0.75 mg once weekly
• May increase to 1.5 mg once weekly if needed
• No dose adjustment required for renal impairment 1

Exenatide (Twice Daily)

• Initial dose: 5 mcg twice daily
• May increase to 10 mcg twice daily after one month if needed
• Not recommended for eGFR <30 mL/min/1.73 m² 1

Exenatide (Once Weekly)

• Fixed dose: 2 mg once weekly
• Use with caution in moderate renal impairment (eGFR 30-59 mL/min/1.73 m²)
• Not recommended for eGFR <30 mL/min/1.73 m² 1

Lixisenatide

• Initial dose: 10 mcg once daily for 2 weeks
• Increase to 20 mcg once daily after 2 weeks
• Not recommended for eGFR <15 mL/min/1.73 m² 1

Special Considerations for Renal Impairment

• For patients with eGFR <20 mL/min/1.73 m², preferred GLP-1 RAs are:
  • Weekly: dulaglutide, semaglutide
  • Daily: liraglutide 1
• If already on canagliflozin or dapagliflozin, continue for kidney and CV benefits even with low eGFR 1

Handling Missed Doses

• If a dose is missed, patients should resume the once-daily or once-weekly regimen as prescribed with the next scheduled dose
• Do not administer extra doses or increase the dose to make up for missed doses
• If more than 3 days have elapsed since the last dose (for daily medications like liraglutide), reinitiate at the lowest dose to mitigate gastrointestinal symptoms 2

Common Adverse Effects and Management

• Gastrointestinal effects (nausea, vomiting, diarrhea) are common but typically transient
• Slow titration is key to minimizing these effects
• Monitor for signs of pancreatitis, gallbladder disease, and thyroid C-cell tumors
• Regular assessment of kidney function (eGFR) is recommended every 3-6 months

Contraindications

• Personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Serious hypersensitivity to the specific GLP-1 RA or its components
• Active acute pancreatitis 1, 2

By following these dosing recommendations and monitoring guidelines, clinicians can optimize the benefits of GLP-1 receptor agonist therapy while minimizing adverse effects for patients requiring this treatment.