Semaglutide Dosing for Weight Loss
The recommended dose of semaglutide for weight loss is 2.4 mg once weekly by subcutaneous injection, with a gradual dose titration schedule to minimize gastrointestinal side effects. 1
Dosing and Titration Schedule
- Semaglutide should be started at 0.25 mg weekly for the first 4 weeks 2
- Then increase to 0.5 mg weekly for 4 weeks 2
- Then increase to 1.0 mg weekly for 4 weeks 2
- Then increase to 1.7 mg weekly for 4 weeks 2
- Finally, reach the maintenance dose of 2.4 mg weekly after 16 weeks 2
Rationale for Dose Selection
- The 2.4 mg weekly dose was established through clinical trials showing superior weight loss compared to lower doses 1, 3
- In the STEP 1 trial, semaglutide 2.4 mg weekly demonstrated mean weight loss of 14.9% at 68 weeks (versus 2.4% with placebo) 1, 3
- Higher doses (up to 16 mg) have been studied but provide only modest additional benefit with significantly more adverse effects 4
Dose Adjustment Considerations
- If a patient misses 2 consecutive doses, clinical judgment is required for subsequent dosing 2
- For patients who tolerated the medication well, resuming at the same dose can be considered 2
- If 3 or more consecutive doses are missed, consider restarting the titration schedule 2
- Some patients may achieve strong response at submaximal doses and could continue at that dose long-term 2
Side Effects Management
- Gastrointestinal adverse effects are the most common side effects (particularly nausea and vomiting) 1, 5, 3
- Gradual dose titration is essential to mitigate these gastrointestinal side effects 2, 1
- Most gastrointestinal side effects are transient, mild-to-moderate in severity, and typically resolve without discontinuation 3
- In clinical trials, approximately 4.5% of participants discontinued treatment due to gastrointestinal events 3
Special Considerations
- Semaglutide should not be used with other GLP-1 receptor agonists or dipeptidyl peptidase-4 inhibitors 2
- Caution is advised when using semaglutide with insulin or insulin secretagogues due to potential hypoglycemia risk 2
- Semaglutide is contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 1
- Weight loss appears to be lower in individuals with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%) 1, 6
Long-term Use
- Semaglutide must be used long-term, as cessation leads to significant weight regain (approximately 11.6% of lost weight regained after stopping treatment) 1, 6
- The medication should be used in conjunction with lifestyle interventions including a hypocaloric diet and increased physical activity 1, 6
Monitoring Recommendations
- Monitor for gastrointestinal adverse effects, particularly during dose escalation 1, 6
- Monitor blood pressure as weight loss progresses, as antihypertensive medication requirements may decrease 1
- Be vigilant for signs of gallbladder disease or pancreatitis, which are rare but reported adverse effects 1