What is the starting dose of semaglutide (glucagon-like peptide-1 (GLP-1) receptor agonist) for weight loss?

Starting Dose of Semaglutide for Weight Loss

The starting dose of semaglutide for weight loss is 0.25 mg subcutaneously once weekly for the first 4 weeks, followed by gradual dose escalation. 1, 2

Dose Titration Schedule

Semaglutide requires a specific titration schedule to minimize gastrointestinal side effects:

• Week 1-4: 0.25 mg subcutaneously once weekly
• Week 5-8: 0.5 mg subcutaneously once weekly
• Week 9-12: 1.0 mg subcutaneously once weekly
• Week 13-16: 1.7 mg subcutaneously once weekly
• Week 17 onward: 2.4 mg subcutaneously once weekly (maintenance dose) 1

This gradual titration approach is essential as it significantly reduces the risk of gastrointestinal adverse effects, which are the most common side effects of semaglutide.

Evidence for Efficacy

The 2.4 mg maintenance dose of semaglutide has demonstrated substantial efficacy for weight loss:

• Mean weight loss of 14.9% from baseline at 68 weeks (compared to 2.4% with placebo) 3
• 86.4% of patients achieve ≥5% weight loss 3
• 69.1% achieve ≥10% weight loss 3
• 50.5% achieve ≥15% weight loss 3

Considerations for Dose Adjustment

• Clinical judgment should guide adjustments to the titration schedule based on individual patient response, tolerance, and adverse effects 1
• If a patient misses 2 consecutive doses, clinical judgment is required for subsequent dosing 1
• If a patient has tolerated the medication well, resuming at the same dose can be considered 1
• If 3 or more consecutive doses are missed, restarting the titration schedule should be considered 1
• Some patients may achieve strong response at submaximal doses (e.g., 1 mg weekly) and could continue at that dose long-term 1, 4, 5

Common Adverse Effects and Management

Gastrointestinal side effects are most common:

• Nausea (44%)
• Diarrhea (32%)
• Constipation (23%)
• Vomiting (25%) 1

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

Important Precautions

• Semaglutide is contraindicated in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 1, 6
• Use with caution in patients with history of pancreatitis or gallbladder disease 6
• Monitor for hypoglycemia if used with insulin or insulin secretagogues 1
• Semaglutide may delay gastric emptying, potentially affecting absorption of other oral medications 1

Real-World Considerations

Recent real-world studies show that even lower maintenance doses (0.5-1.0 mg weekly) can be effective:

• A study using 0.5-1.0 mg weekly showed 6.15% weight loss at 12 weeks 5
• Another study found similar weight loss with 1.0 mg (13.6%) and 2.0 mg (12.8%) at 6 months 4

This suggests that some patients may achieve satisfactory results with lower maintenance doses, potentially reducing side effects and cost.

The key to successful treatment is adherence to the gradual titration schedule, which significantly improves tolerability while maximizing effectiveness for weight loss.