What is the recommended dosing regimen for semaglutide (glucagon-like peptide-1 receptor agonist) for weight loss?

Semaglutide Dosing Regimen for Weight Loss

For weight loss in adults, semaglutide should be initiated at 0.25 mg subcutaneously once weekly for 4 weeks, then increased to 0.5 mg weekly for 4 weeks, with gradual titration to a maintenance dose of 2.4 mg weekly. 1

Patient Selection

• Indicated for adults with:
  • BMI ≥30 kg/m² (obesity), or
  • BMI ≥27 kg/m² with at least one weight-related comorbidity 1
• Documentation should include obesity as a medical condition and failure of previous weight loss attempts with lifestyle modifications 1

Detailed Dosing Protocol

1. Initial dose: 0.25 mg subcutaneously once weekly for weeks 1-4
2. First titration: 0.5 mg weekly for weeks 5-8
3. Second titration: 1.0 mg weekly for 4 weeks
4. Third titration: 1.7 mg weekly for 4 weeks
5. Maintenance dose: 2.4 mg weekly 1, 2

This gradual titration schedule is essential to minimize gastrointestinal side effects, which are the most common adverse events.

Efficacy

• Semaglutide 2.4 mg weekly produces clinically significant weight loss:
  • Mean weight reduction of 14.9-16.0% at 68 weeks 1, 2
  • 86.4% of patients achieve ≥5% weight loss
  • 69.1% achieve ≥10% weight loss
  • 50.5% achieve ≥15% weight loss 2

Administration Considerations

• Administer subcutaneously once weekly at any time of day, with or without meals
• Can be injected in the abdomen, thigh, or upper arm
• Should be used in conjunction with lifestyle interventions (reduced-calorie diet and increased physical activity) 1

Monitoring and Discontinuation

• Evaluate weight loss after 12-16 weeks at the maintenance dose
• Consider discontinuation if <5% weight reduction is not achieved at this point 1
• Monitor for side effects, particularly gastrointestinal symptoms

Safety and Side Effects

• Most common adverse events are gastrointestinal:
  • Nausea (reported in up to 74.2% of users)
  • Vomiting
  • Diarrhea
  • Dyspepsia
  • Reflux 1, 3
• These side effects are typically transient, mild-to-moderate in severity, and subside with time 2
• Approximately 4.5% of patients discontinue treatment due to gastrointestinal events 2

Important Contraindications

• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2
• Pregnancy
• Use with caution in patients with history of pancreatitis or gallbladder disease 1

Special Considerations

• No dosage adjustments required for patients with renal impairment 4
• Delayed gastric emptying may affect absorption of concomitantly administered oral medications 5
• Not studied in pediatric patients 5

Clinical Pearl

The weight loss efficacy of semaglutide is significantly greater than previous weight management medications, with mean weight reductions of approximately 15% at 68 weeks, making it one of the most effective pharmacological options for obesity treatment currently available 6. However, weight regain is common if treatment is discontinued, highlighting the importance of continued therapy for weight maintenance 7.