What is the recommended protocol for initiating GLP-1 (Glucagon-like peptide-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic), for weight loss?

GLP-1 Receptor Agonist Initiation Protocol for Weight Loss

For weight loss, GLP-1 receptor agonists should be initiated at low doses and gradually titrated upward following a specific schedule to minimize gastrointestinal side effects and optimize efficacy. 1, 2

Patient Selection

• Appropriate candidates:

  • BMI ≥30 kg/m² or
  • BMI ≥27 kg/m² with weight-related comorbidities 2

• Contraindications:

  • Personal or family history of medullary thyroid carcinoma
  • Multiple endocrine neoplasia syndrome type 2
  • Pregnancy or planning pregnancy
  • History of pancreatitis (precaution) 2

Medication-Specific Titration Protocols

Semaglutide (Ozempic/Wegovy)

• Starting dose: 0.25 mg subcutaneously once weekly for 4 weeks 3
• Week 5-8: Increase to 0.5 mg once weekly
• Week 9-12: Increase to 1.0 mg once weekly (if additional weight loss needed)
• For Wegovy (2.4 mg formulation): Continue titration to 1.7 mg and then 2.4 mg at 4-week intervals 2
• Administer on the same day each week, with or without meals 3

Liraglutide (Saxenda)

• Starting dose: 0.6 mg subcutaneously once daily for 1 week 4, 1
• Week 2: Increase to 1.2 mg once daily
• Week 3: Increase to 1.8 mg once daily (if additional weight loss needed)
• For Saxenda (3.0 mg formulation): Continue weekly 0.6 mg increases until reaching 3.0 mg 1
• Administer at any time of day, independent of meals 4

Administration Guidelines

• Injection sites: Abdomen, thigh, or upper arm
• Rotate injection sites within the same region to reduce risk of cutaneous amyloidosis 4, 3
• Inspect solution before use (should be clear, colorless, and free of particles)
• If using with insulin, administer as separate injections (never mix) 4, 3

Monitoring Protocol

• Evaluate weight loss at 16 weeks on maintenance dose:
  • Continue therapy if ≥5% weight reduction achieved
  • Discontinue if <5% weight reduction achieved 2
• Early responders (>5% weight loss in first 3 months) typically have better long-term outcomes 2

Managing Common Side Effects

• Gastrointestinal symptoms (most common):

  • Nausea: 17-44% with semaglutide, 8% with liraglutide
  • Diarrhea: 16-32% with semaglutide, 9% with liraglutide
  • Constipation: 10-23% with semaglutide, 5% with liraglutide
  • Vomiting: 7-25% with semaglutide, 4% with liraglutide 1, 2

• Management strategies:

  • Slow titration (follow recommended schedule)
  • Reduce meal size
  • Limit alcohol and carbonated drinks
  • Avoid high-fat diets 2

Expected Outcomes

• Semaglutide: 14.9-16.0% mean weight loss at 68 weeks
• Liraglutide: 3.6-7.8% mean weight loss 1, 2, 5
• Tirzepatide: 15.0-20.9% mean weight loss at 72 weeks (if available) 1, 2

Important Considerations

• If a dose is missed:

  • Semaglutide: Administer within 5 days; if >5 days have passed, skip and resume regular schedule 3
  • Liraglutide: Resume once-daily dosage with next scheduled dose; if >3 days missed, reinitiate at 0.6 mg 4

• Nutritional support:

  • Monitor for nutritional deficiencies due to reduced caloric intake
  • Implement resistance training to preserve muscle mass 6

• Cost considerations:

  • Semaglutide 2.4 mg (Wegovy): ~$1,300-1,600 for 30-day supply
  • Insurance coverage may be limited 2

By following this structured protocol for GLP-1 receptor agonist initiation, you can maximize weight loss outcomes while minimizing adverse effects for your patients.