What is the recommended dosing regimen for semaglutide (Glucagon-Like Peptide-1 (GLP-1) receptor agonist) for weight loss?

Semaglutide Dosing Regimen for Weight Loss

For optimal weight loss outcomes, semaglutide should be initiated at 0.25 mg weekly for the first 4 weeks, followed by dose escalation 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, 2

Recommended Titration Schedule

The gradual dose titration of semaglutide is essential to minimize gastrointestinal adverse effects:

1. Week 1-4: 0.25 mg weekly
2. Week 5-8: 0.5 mg weekly
3. Week 9-12: 1.0 mg weekly
4. Week 13-16: 1.7 mg weekly
5. Week 17 onwards: 2.4 mg weekly (maintenance dose)

This titration schedule allows patients to adjust to the medication gradually, reducing the likelihood of discontinuation due to adverse effects 1.

Efficacy of Semaglutide for Weight Loss

Semaglutide at the 2.4 mg weekly dose has demonstrated substantial weight loss efficacy:

• Mean weight reduction of 14.9-16.0% at 68 weeks with 2.4 mg weekly dosing 2, 3
• Significantly greater weight loss compared to placebo (12.4 percentage points difference) 3
• High proportion of patients achieving clinically significant weight loss:
  • 86.4% achieve ≥5% weight loss
  • 69.1% achieve ≥10% weight loss
  • 50.5% achieve ≥15% weight loss 3

Mechanism of Action

Semaglutide promotes weight loss through several mechanisms:

• Delays gastric emptying
• Reduces hunger and food cravings
• Enhances feelings of fullness after meals through improved satiety signals
• Acts on GLP-1 receptors in the hypothalamus to regulate appetite 2, 4

Studies show that semaglutide reduces ad libitum energy intake by approximately 24%, with improved control of eating and lower preference for high-fat foods 4.

Special Clinical Considerations

Missed Doses

• If 1-2 consecutive doses are missed: Clinical judgment is required; resuming at the same dose can be considered if the patient has tolerated the medication well
• If 3 or more consecutive doses are missed: Consider restarting the titration schedule 1

Submaximal Dosing

Some patients may achieve a strong response at a submaximal dose (before reaching 2.4 mg) and could continue at that dose long-term 1.

Drug Interactions

• Semaglutide should not be used with other GLP-1 receptor agonists or dipeptidyl peptidase-4 inhibitors
• May delay gastric emptying, potentially impacting absorption of oral medications requiring rapid onset of action
• Use with caution in combination with insulin or insulin secretagogues; monitor for hypoglycemia 1, 2

Adverse Effects and Management

The most common adverse effects are gastrointestinal:

• Nausea (most common)
• Vomiting
• Diarrhea
• Constipation

These effects are typically transient, mild-to-moderate in severity, and subside with time 3, 5. The gradual dose titration schedule significantly helps minimize these effects.

Monitoring Recommendations

• Assess effectiveness and safety monthly for the first 3 months, then quarterly thereafter
• Early response (>5% weight loss after 3 months) predicts improved long-term outcomes
• If inadequate response (<5% weight loss after 3 months), reevaluate the treatment approach 2

Treatment Duration

For sustained weight management, semaglutide treatment should be continued indefinitely in patients who respond well, as significant weight regain occurs after discontinuation 2.

Cautions and Contraindications

• Contraindicated in pregnancy
• Use with caution in patients with history of pancreatitis or gallbladder disease
• Contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 2, 6

Population Considerations

Semaglutide has demonstrated efficacy across diverse populations, including East Asian populations where a 13.2% mean weight reduction was observed with the 2.4 mg dose 7.