What is the typical maintenance dose for patients on Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide (Victoza), semaglutide (Ozempic), or dulaglutide (Trulicity)?

GLP-1 Receptor Agonist Maintenance Dosing

The typical maintenance doses for GLP-1 receptor agonists are: liraglutide 1.8 mg daily, semaglutide 1.0 mg weekly (injectable) or 14 mg daily (oral), and dulaglutide 1.5 mg weekly, with higher doses available for some agents when additional glycemic control is needed. 1, 2

Maintenance Doses by Specific GLP-1 Receptor Agonist

Liraglutide (Victoza)

• Starting dose: 0.6 mg daily for 1 week
• Titration: 1.2 mg daily for 1 week
• Maintenance dose: 1.8 mg daily
• Administration: Once-daily subcutaneous injection
• No dose adjustment required for renal impairment down to eGFR 15 ml/min/1.73 m² 1

Semaglutide Injectable (Ozempic)

• Starting dose: 0.25 mg weekly for 4 weeks
• First titration: 0.5 mg weekly
• Maintenance dose: 1.0 mg weekly
• Higher dose option: 2.4 mg weekly (for additional glycemic control)
• Administration: Once-weekly subcutaneous injection
• No dose adjustment required for eGFR ≥30 ml/min/1.73 m² 1, 2

Semaglutide Oral (Rybelsus)

• Starting dose: 3 mg daily for 30 days
• First titration: 7 mg daily
• Maintenance dose: 14 mg daily if additional glycemic control needed
• Administration: Once-daily oral tablet taken on empty stomach with water only, 30 minutes before first food/beverage/medication 2

Dulaglutide (Trulicity)

• Starting dose: 0.75 mg weekly
• Maintenance dose: 1.5 mg weekly
• Higher dose options: 3 mg and 4.5 mg weekly (for additional glycemic control)
• Administration: Once-weekly subcutaneous injection
• No dose adjustment required for renal impairment 1, 3

Titration Principles

Proper titration is essential to minimize gastrointestinal side effects and optimize efficacy:

1. Start low: All GLP-1 RAs require starting at a lower dose
2. Gradual titration: Increase dose at recommended intervals (weekly or monthly depending on agent)
3. Assess tolerability: Monitor for GI side effects before each dose increase
4. Optimize dose: Titrate to the maintenance dose that provides adequate glycemic control with acceptable side effects 2

Considerations for Dose Selection

• Efficacy: Higher maintenance doses generally provide greater HbA1c reduction and weight loss

  • Semaglutide 1.0 mg weekly provides 7.0% weight loss vs. 3.4% with placebo 1
  • Dulaglutide 1.5 mg weekly provides greater HbA1c reduction (-1.1%) compared to 0.75 mg (-0.9%) 3

• Side effect profile: Higher doses may increase GI side effects

  • Common adverse events include nausea (up to 20%), vomiting, and diarrhea 2
  • Side effects typically diminish over time with continued treatment

• Renal function: Most GLP-1 RAs can be used without dose adjustment in reduced renal function

  • Dulaglutide and liraglutide require no dose adjustment even with eGFR down to 15 ml/min/1.73 m² 1

Clinical Pearls

• Dose optimization: If glycemic targets are not met on the standard maintenance dose, consider titrating to the highest approved dose before switching agents

  • For dulaglutide, doses up to 4.5 mg weekly provide additional HbA1c reduction (-1.8%) compared to 1.5 mg (-1.5%) 3

• Switching between agents: When switching from one GLP-1 RA to another:

  • Semaglutide provides better glycemic control (-0.42%) and weight reduction (-2.6 kg) compared to dulaglutide when switching from liraglutide 4
  • No washout period is typically needed when switching between GLP-1 RAs

• Combination therapy: When combining with insulin or sulfonylureas, consider reducing doses of these agents to minimize hypoglycemia risk 3

• Monitoring: Assess glycemic response 2-4 weeks after reaching maintenance dose to determine if dose adjustment is needed 2

Remember that while these are the typical maintenance doses, individual response may vary, and dose adjustments should be based on glycemic control, weight effects, and tolerability.