What is the recommended dosage and administration of semaglutide (glucagon-like peptide-1 (GLP-1) receptor agonist) for weight loss?

Semaglutide Dosage and Administration for Weight Loss

For weight loss in adults with obesity or overweight with weight-related comorbidities, semaglutide should be administered at a target dose of 2.4 mg subcutaneously once weekly, following a gradual dose titration schedule to minimize gastrointestinal side effects. 1

Dosing Schedule and Titration

The recommended titration schedule for semaglutide for weight management is:

1. Start at 0.25 mg once weekly for 4 weeks
2. Increase to 0.5 mg once weekly for 4 weeks
3. Increase to 1.0 mg once weekly for 4 weeks
4. Increase to 1.7 mg once weekly for 4 weeks
5. Reach maintenance dose of 2.4 mg once weekly by week 16 1

This gradual titration is essential to minimize gastrointestinal adverse effects, which are the most common side effects of semaglutide.

Administration Guidelines

• Administer subcutaneously in the abdomen, thigh, or upper arm 2
• Can be administered at any time of day, with or without meals 2
• If a dose is missed, administer within 5 days of the missed dose 2

Efficacy for Weight Loss

Semaglutide 2.4 mg weekly has demonstrated superior weight loss outcomes compared to other GLP-1 receptor agonists:

• Mean weight loss of 14.9% from baseline at 68 weeks (vs. 2.4% with placebo) 3, 1
• 86.4% of patients achieve ≥5% weight loss 3
• 69.1% achieve ≥10% weight loss 3
• 50.5% achieve ≥15% weight loss 3

The most recent meta-analysis shows that semaglutide produces a weighted mean difference of -12.1% in body weight compared to placebo, with 33.4% of participants achieving ≥20% weight loss 4.

Clinical Considerations

Monitoring and Continuation Criteria

• Evaluate response after 16 weeks at the maintenance dose
• If a patient has not lost at least 5% of baseline body weight after 16 weeks on the 2.4 mg dose, consider discontinuation 1

Special Populations

• No dosage adjustments required for patients with renal impairment 1
• Can be used in patients with eGFR of 2 mL/min per 1.73 m² or lower or UACR of 30 mg/g or higher 1

Missed Doses

• If more than 2 consecutive doses are missed, clinical judgment is required for subsequent dosing 1
• If a patient has tolerated the medication well, resuming at the same dose can be considered
• Otherwise, consider lowering the next dose
• If 3 or more consecutive doses are missed, consider restarting the titration schedule 1

Common Side Effects and Management

The most common adverse events are gastrointestinal:

• Nausea (most common)
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain 1, 3

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

Important Precautions

• Contraindicated in:

  • Pregnancy and breastfeeding
  • Personal or family history of medullary thyroid cancer or MEN2 1

• Use with caution in patients with:

  • History of pancreatitis
  • Cholelithiasis
  • Severe renal impairment (due to potential risk from vomiting and dehydration) 1

• Drug interactions:

  • Should not be used with other GLP-1 receptor agonists or dipeptidyl peptidase-4 inhibitors
  • May delay gastric emptying, potentially affecting absorption of other oral medications
  • Use caution when combining with insulin or insulin secretagogues due to hypoglycemia risk 1

Long-term Considerations

Weight regain is common after discontinuation of semaglutide, suggesting that long-term use is necessary for sustained weight management 1. In studies where participants were followed for an additional 52 weeks after completing 68 weeks of semaglutide treatment, mean weight regain was 11.6% of lost weight 1.