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

Dosing Schedule and Titration

The recommended dosing schedule for semaglutide when used for weight loss follows a gradual titration approach:

• 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)

This gradual titration is essential to minimize gastrointestinal adverse effects, which are the most common side effects associated with semaglutide 1, 2.

Efficacy at Target Dose

At the maintenance dose of 2.4 mg weekly, semaglutide has demonstrated substantial weight loss efficacy:

• Mean weight loss of 14.9-16.0% at 68 weeks 1
• 86.4% of patients achieve ≥5% weight loss
• 69.1% achieve ≥10% weight loss
• 50.5% achieve ≥15% weight loss 2

This significantly exceeds the weight loss seen with other GLP-1 receptor agonists such as liraglutide, which achieves approximately 8.0% weight loss at 56 weeks 1.

Missed Dose Management

If 1-2 consecutive doses are missed, clinical judgment is required:

• Resume at the same dose if the patient has tolerated the medication well
• If 3 or more consecutive doses are missed, consider restarting the titration schedule 1

Submaximal Dosing Consideration

Some patients may achieve a strong response at a dose lower than 2.4 mg. In such cases, continuing at that submaximal dose long-term is reasonable 1. This approach may help minimize side effects while maintaining efficacy.

Monitoring and Assessment

• Evaluate 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
• Continue medication if patient achieves ≥5% weight loss after the initial 3-month period 1

Important Contraindications and Precautions

• Not to 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
• Contraindicated in pregnancy and in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 1

Common Adverse Effects

The most common adverse effects are gastrointestinal:

• Nausea, vomiting, diarrhea, and constipation
• These are typically transient, mild-to-moderate in severity, and subside with time
• Gradual dose titration helps mitigate these adverse effects 1, 2

Duration of Treatment

For sustained weight management, semaglutide treatment should be continued indefinitely in patients who respond well, as significant weight regain occurs after discontinuation 1.

Additional Health Benefits

Beyond weight loss, semaglutide offers several additional health benefits:

• 20% reduction in risk of cardiovascular death, heart attacks, and strokes in adults with obesity or overweight and cardiovascular disease
• Potential benefits for patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) 1

The evidence strongly supports the use of semaglutide at a target dose of 2.4 mg weekly for weight loss, with a structured titration schedule to optimize both efficacy and tolerability.