What is the typical dosing regimen for terzipatide (glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist) for weight loss?

Tirzepatide Dosing for Weight Loss

Start tirzepatide at 2.5 mg subcutaneously once weekly and escalate the dose every 4 weeks through 5 mg, 7.5 mg, 10 mg, and 12.5 mg to reach a maximum maintenance dose of 15 mg weekly for optimal weight loss. 1

Dose Escalation Schedule

The FDA-approved titration protocol is designed to minimize gastrointestinal side effects while maximizing efficacy 1:

• Week 1-4: 2.5 mg once weekly (initiation dose only, not for maintenance) 1
• Week 5-8: 5 mg once weekly 1
• Week 9-12: 7.5 mg once weekly 2
• Week 13-16: 10 mg once weekly 2
• Week 17-20: 12.5 mg once weekly 2
• Week 21 onward: 15 mg once weekly (maximum dose) 1

Each dose increase should occur after at least 4 weeks on the current dose, with adjustments based on individual tolerability 1.

Maintenance Dosing Options

For weight reduction and long-term maintenance: The recommended maintenance doses are 5 mg, 10 mg, or 15 mg once weekly 1. The 15 mg dose produces maximum efficacy and should be the target for most patients unless tolerability issues arise 2.

For obstructive sleep apnea: The recommended maintenance doses are 10 mg or 15 mg once weekly 1.

Dose-Dependent Efficacy

Tirzepatide demonstrates clear dose-response relationships at 72 weeks 2:

• 5 mg weekly: 15.0% mean weight loss 2
• 10 mg weekly: 19.5% mean weight loss 2
• 15 mg weekly: 20.9% mean weight loss (maximum efficacy) 2
• Placebo: 3.1% weight loss 3

Between 20.7-68.4% of patients achieve ≥10% total body weight loss, with nearly 40% on the 15 mg dose achieving ≥25% weight loss 2, 4.

Patient Selection Criteria

Eligible patients include 2, 3:

• BMI ≥30 kg/m² (obesity), OR
• BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease)

Absolute contraindications 2, 1:

• Personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2
• Known serious hypersensitivity to tirzepatide

Administration Details

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

Missed Dose Management

If a dose is missed 1:

• Administer as soon as possible within 4 days (96 hours) of the missed dose
• If >4 days have passed, skip the missed dose and resume regular schedule
• The day of weekly administration can be changed if at least 3 days (72 hours) separate doses

Monitoring Schedule

First 3 months: Assess effectiveness and safety at least monthly 2

After 3 months: Continue monitoring at least quarterly 2

Specific parameters to monitor 2:

• Weight and BMI
• Blood pressure (tirzepatide may cause elevated heart rate)
• Gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation)
• Signs of cholelithiasis and gallstone-related complications
• Delayed absorption of oral medications with narrow therapeutic indices

Managing Gastrointestinal Side Effects

The most common adverse events are gastrointestinal, including nausea (31%), diarrhea (23%), vomiting (12%), and constipation (5%) 4. These are typically mild-to-moderate and transient 5.

Management strategies 3:

• Use the slow upward titration schedule as prescribed
• Reduce meal size
• Limit alcohol and carbonated drinks
• Avoid high-fat diets

If patients cannot tolerate a maintenance dose, consider stepping down to a lower maintenance dose 1.

Treatment Evaluation and Discontinuation

Evaluate treatment efficacy at 12-16 weeks on the maximum tolerated dose 4. Consider discontinuing tirzepatide if there is <4-5% body weight loss at 16 weeks, extrapolating from guidelines for other GLP-1 receptor agonists 4.

Long-Term Considerations

Long-term use is necessary to maintain weight loss benefits—discontinuation leads to rapid weight regain 4. Tirzepatide must be continued indefinitely for sustained weight management 4.

Comparative Efficacy

Tirzepatide is superior to other weight loss medications 2, 3:

• Produces 5.5 kg more weight loss than semaglutide 1.0 mg at 40 weeks 3
• Achieves 20.2% mean weight reduction versus 13.7% with semaglutide at 72 weeks 4
• Weight loss efficacy is comparable to bariatric surgery outcomes 4, 3

Cost Considerations

The average wholesale price is $1,272 per 30-day supply, with national average drug acquisition cost of $1,017 2, 3. Insurance coverage varies and may influence treatment decisions 3.