What is the recommended dosing regimen for zepbound (tirzepatide) for weight loss?

Tirzepatide (Zepbound) Dosing Protocol for Weight Loss

The recommended dosing regimen for Zepbound (tirzepatide) starts with 2.5 mg subcutaneously once weekly for 4 weeks, then increases to 5 mg weekly, with further dose escalation in 2.5 mg increments every 4 weeks as tolerated, up to a maximum of 15 mg weekly. 1

Initial Dosing and Titration Schedule

• Starting dose: 2.5 mg subcutaneously once weekly for 4 weeks

  • Note: The 2.5 mg dose is for initiation only and not approved as a maintenance dose 1

• First escalation: Increase to 5 mg once weekly after the initial 4 weeks

• Further escalation: May increase dose in 2.5 mg increments (to 7.5 mg, 10 mg, 12.5 mg, and 15 mg) at intervals of at least 4 weeks on the current dose 1

• Maintenance dose: 5 mg, 10 mg, or 15 mg once weekly, based on treatment response and tolerability 1

• Maximum dose: 15 mg once weekly 1

Administration Guidelines

• Administer subcutaneously in the abdomen, thigh, or upper arm
• Rotate injection sites with each dose
• Can be administered at any time of day, with or without meals 1
• Must be used in combination with reduced-calorie diet and increased physical activity 1

Missed Dose Management

• If a dose is missed, administer as soon as possible within 4 days (96 hours) after the missed dose
• If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day
• The day of weekly administration can be changed if necessary, as long as the time between doses is at least 3 days (72 hours) 1

Efficacy Considerations

Tirzepatide has demonstrated superior weight loss compared to other medications:

• Mean weight reduction of 20.9% from baseline (vs. 3.1% with placebo) in clinical trials 2
• 91% of patients on the 15 mg dose achieved ≥5% weight reduction 2
• 57% of patients on the 15 mg dose achieved ≥20% weight reduction 2
• Tirzepatide showed superior weight reduction compared to semaglutide (-20.2% vs -13.7%) 3

Side Effect Management

The most common adverse events are gastrointestinal, occurring primarily during dose escalation:

• Nausea, diarrhea, vomiting, and constipation 2
• Most side effects are mild to moderate in severity 2

To minimize gastrointestinal side effects:

• Follow the recommended gradual dose escalation schedule
• Consider reducing meal size
• Avoid high-fat foods
• Limit alcohol and carbonated drinks 4
• If patients don't tolerate a maintenance dose, consider a lower maintenance dose 1

Special Considerations

• Contraception: Patients using oral hormonal contraception should use or add a non-oral method for 4 weeks after initiation and dose escalations 4

• Perioperative management: Consider the long half-life of tirzepatide (5 days) when planning surgery 4

• Long-term therapy: Weight regain is likely if medication is discontinued, suggesting a need for long-term treatment 4

• Comorbidity management: Monitor for potential reduction in medication needs for comorbidities as weight loss progresses 4

Monitoring Recommendations

• Assess efficacy and safety at least monthly for the first 3 months and at least quarterly thereafter 5
• Early response (typically >5% weight loss after 3 months) predicts better long-term outcomes 5
• If early use appears ineffective (<5% weight loss after 3 months), consider discontinuing and exploring other treatment options 5

By following this structured titration protocol and monitoring plan, you can optimize the efficacy of tirzepatide while minimizing side effects for patients using it for weight loss.