What is the recommended starting dose of semaglutide (glucagon-like peptide-1 receptor agonist) for an adult patient with type 2 diabetes or obesity?

Semaglutide Starting Dose

Start semaglutide at 0.25 mg subcutaneously once weekly for the first 4 weeks, then escalate to 0.5 mg weekly, regardless of whether treating type 2 diabetes or obesity. 1

Dosing Algorithm by Indication

For Type 2 Diabetes

• Week 0-4: 0.25 mg once weekly 1
• Week 5+: 0.5 mg once weekly 1
• If additional glycemic control needed after ≥4 weeks at 0.5 mg: Escalate to 1.0 mg once weekly 1
• Maximum approved dose for diabetes: 2.0 mg once weekly (though 1.0 mg is standard maintenance) 2

For Obesity/Weight Management

• Week 0-4: 0.25 mg once weekly 3, 4
• Week 5-8: 0.5 mg once weekly 3, 4
• Week 9-12: 1.0 mg once weekly 3, 4
• Week 13-16: 1.7 mg once weekly 3, 4
• Week 17+: 2.4 mg once weekly (maintenance dose) 3, 4

Administration Details

• Inject subcutaneously in abdomen, thigh, or upper arm 1
• Administer at any time of day, with or without meals 1
• If a dose is missed, administer within 5 days of the missed dose 1

Critical Titration Principles

Gradual dose escalation is mandatory to minimize gastrointestinal adverse events, which occur in 44% of patients (nausea), 32% (diarrhea), and 25% (vomiting) at maximum doses. 3 Recent evidence demonstrates that slower titration significantly improves adherence: only 2% of patients withdrew due to gastrointestinal side effects with flexible gradual titration versus 19% with standard label-recommended titration. 5

Managing Gastrointestinal Symptoms During Titration

• If nausea or vomiting are severe, maintain the current dose for an additional 4 weeks before advancing rather than discontinuing therapy 3, 4
• Gastrointestinal symptoms typically diminish over time and rarely require permanent discontinuation 6
• Some patients achieve strong glycemic and weight responses at submaximal doses and can continue long-term at lower maintenance doses 4

Mandatory Concomitant Interventions

• Implement caloric deficit of at least 500 kcal/day below total energy requirements 3
• Prescribe minimum 150 minutes weekly of structured physical activity 3
• Provide ongoing behavioral counseling for dietary modifications 3

Monitoring Requirements

• Body weight: Every 4 weeks during dose escalation 3, 6
• Gastrointestinal symptoms: Assess at each visit 3, 6
• Glucose levels (if diabetic): Monitor more frequently during titration, especially if using concomitant insulin or sulfonylureas 3, 6, 4

Drug Interaction Precautions

• Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 4
• Reduce insulin or sulfonylurea doses when initiating semaglutide to prevent hypoglycemia 6, 4
• Semaglutide delays gastric emptying, potentially affecting absorption of oral medications requiring rapid onset 4

Common Pitfall to Avoid

The most common error is advancing doses too rapidly despite persistent gastrointestinal symptoms. The correct approach is to extend the duration at the current dose rather than discontinue therapy, as symptoms typically resolve with time and slow titration is the most effective mitigation strategy. 3, 5