What is the recommended dose and treatment course for semaglutide (glucagon-like peptide-1 receptor agonist) for weight loss?

Semaglutide Dosing for Weight Management

For weight loss, semaglutide should be initiated at 0.25 mg weekly for the first 4 weeks, then increased to 0.5 mg, 1.0 mg, and 1.7 mg weekly every 4 weeks, until reaching the maintenance dose of 2.4 mg after 16 weeks. 1

Dosing Schedule and Administration

• Semaglutide is administered as a once-weekly subcutaneous injection 1
• The recommended titration schedule to minimize gastrointestinal side effects is:
  • Week 1-4: 0.25 mg once weekly
  • Week 5-8: 0.5 mg once weekly
  • Week 9-12: 1.0 mg once weekly
  • Week 13-16: 1.7 mg once weekly
  • Week 17 onwards: 2.4 mg once weekly (maintenance dose) 1
• The full maintenance dose of 2.4 mg weekly is FDA-approved specifically for weight management 1
• Clinical judgment should be used to adjust the titration schedule based on individual patient response, tolerance, and adverse effects 1

Duration of Treatment

• Semaglutide should be considered a long-term medication for chronic weight management 1, 2
• Studies show significant weight regain occurs after discontinuation, suggesting ongoing treatment is necessary for sustained weight loss 1
• In clinical trials, participants followed for 52 weeks after completing 68 weeks of semaglutide treatment experienced mean weight regain of 11.6% of lost weight 1

Efficacy

• At the 2.4 mg maintenance dose, semaglutide produces mean weight loss of 10.8-14.9% of total body weight after 52-72 weeks 1, 2
• Clinical trials demonstrate:
  • 86.4% of patients achieve ≥5% weight loss
  • 69.1% achieve ≥10% weight loss
  • 50.5% achieve ≥15% weight loss 2
• Weight loss with semaglutide is significantly greater than with liraglutide (13.8% vs 7.8%) 3
• Semaglutide must be used in conjunction with lifestyle interventions including reduced-calorie diet and increased physical activity 1

Special Considerations

Missed Doses

• If 1-2 consecutive doses are missed, patients may resume at the same dose if previously well-tolerated 1
• If 3 or more consecutive doses are missed, consider restarting the titration schedule 1
• Some patients may achieve strong response at submaximal doses and could continue at that dose long-term 1

Monitoring and Adjustments

• Regular monitoring of gastrointestinal side effects is recommended 1
• Blood pressure and heart rate should be monitored periodically 1
• For patients with diabetes, monitor for hypoglycemia if used with insulin or insulin secretagogues 1

Common Adverse Effects

• Gastrointestinal effects are most common, particularly during dose escalation 1, 2
• Nausea (40% vs 14.8% with placebo) and vomiting (16% vs 4.3% with placebo) are the most frequently reported 1, 2
• Most GI side effects are transient, mild-to-moderate in severity, and typically resolve without discontinuation 2, 4
• Serious adverse events include rare cases of pancreatitis, gallbladder disease, and delayed gastric emptying 1

Contraindications and Precautions

• Contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 1
• Should not be used with other GLP-1 receptor agonists or dipeptidyl peptidase-4 inhibitors 1
• May delay gastric emptying, potentially affecting absorption of oral medications requiring rapid onset 1
• Use caution in patients undergoing procedures requiring general anesthesia due to increased risk of regurgitation and aspiration 1

By following this structured titration schedule and monitoring for side effects, semaglutide can be effectively used for weight management in appropriate patients, with the understanding that it requires long-term use for sustained benefit.