Is 0.25 mg of Wegovy (semaglutide) every 2 weeks an effective maintenance dose?

Wegovy Maintenance Dose: 0.25 mg Every 2 Weeks is NOT Appropriate

No, 0.25 mg of Wegovy every 2 weeks is not an effective maintenance dose and should not be used. The FDA-approved maintenance dose for Wegovy is 2.4 mg subcutaneously once weekly, reached after a 16-week titration schedule 1, 2.

Standard Dosing Protocol

The evidence-based dosing regimen for Wegovy requires:

• Week 0-4: 0.25 mg once weekly 1, 2
• Week 5-8: 0.5 mg once weekly 1, 2
• Week 9-12: 1.0 mg once weekly 1, 2
• Week 13-16: 1.7 mg once weekly 1, 2
• Week 17 onward: 2.4 mg once weekly (maintenance dose) 1, 2

The 0.25 mg dose is exclusively an initial titration dose, not a maintenance dose. It is used only for the first 4 weeks to minimize gastrointestinal adverse effects 1, 2.

Why 0.25 mg Every 2 Weeks Fails

The proposed regimen of 0.25 mg every 2 weeks is problematic for multiple reasons:

• Insufficient dosing: This provides only 0.5 mg per month, which is 19-fold lower than the therapeutic maintenance dose of 2.4 mg weekly (9.6 mg per month) 1, 2
• No evidence base: Clinical trials demonstrating efficacy used 2.4 mg weekly as the target maintenance dose, achieving mean weight loss of 14.9% at 68 weeks 3
• Subtherapeutic exposure: The 0.25 mg dose was designed only as a starting dose to allow GI tolerance, not to provide therapeutic benefit 1, 2

Clinical Efficacy Data

The STEP 1 trial, which led to FDA approval, demonstrated that 2.4 mg weekly resulted in:

• Mean weight loss of 14.9% versus 2.4% with placebo 3
• 86.4% of participants achieving ≥5% weight loss 3
• 69.1% achieving ≥10% weight loss 3
• 50.5% achieving ≥15% weight loss 3

Real-world data from 8,177 patients using the approved 2.4 mg weekly maintenance dose showed mean weight loss of 17.6% at 12 months and 20.4% at 24 months 4.

Submaximal Dosing Considerations

While some patients may achieve adequate response at submaximal doses (0.5 mg, 1.0 mg, or 1.7 mg weekly), this clinical decision should only be made if:

• The patient has achieved a strong therapeutic response at that dose 1
• The dose is still administered once weekly (not every 2 weeks) 1, 2
• The patient cannot tolerate dose escalation due to adverse effects 1

Even in these scenarios, 0.25 mg remains inappropriate as it is below any recognized therapeutic threshold 1, 2.

Practical Guidance

If a patient cannot tolerate the 2.4 mg maintenance dose:

• Consider maintaining at 1.7 mg, 1.0 mg, or 0.5 mg once weekly if therapeutic benefit is demonstrated 1
• Gradual titration is essential to minimize GI side effects (nausea, vomiting, diarrhea) 1, 2
• If 2 consecutive doses are missed, resume at the same dose if previously well-tolerated, or consider lowering one dose level 1, 2
• If 3+ consecutive doses are missed, restart the titration schedule 1, 2

The dosing interval must remain once weekly—extending to every 2 weeks eliminates therapeutic efficacy 1, 2.