Guidelines for Administering Tirzepatide for Weight Loss
Start tirzepatide at 2.5 mg subcutaneously once weekly and titrate upward every 4 weeks through 5 mg, 7.5 mg, 10 mg, and 12.5 mg to reach the maximum dose of 15 mg weekly, which achieves the greatest weight loss of 20.9% at 72 weeks. 1
Patient Selection Criteria
Prescribe tirzepatide for adults with BMI ≥30 kg/m² (obesity) or BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease). 1
Absolute Contraindications
- Personal or family history of medullary thyroid carcinoma 1
- Multiple Endocrine Neoplasia syndrome type 2 1
- Severe gastrointestinal disease including gastroparesis 1
Use With Caution
- eGFR 15-30 mL/min/1.73 m²: Exercise caution when initiating or escalating doses due to acute kidney injury risk 1
- eGFR <15 mL/min/1.73 m² or dialysis: Avoid use due to limited clinical experience 1
- eGFR >30 mL/min/1.73 m²: No dose adjustment required 1
Dosing Schedule and Administration
Titration Protocol
- Week 0-4: Start at 2.5 mg once weekly (tolerability assessment dose, not therapeutic) 1, 2
- Week 5-8: Increase to 5 mg once weekly 1
- Week 9-12: Increase to 7.5 mg once weekly 1
- Week 13-16: Increase to 10 mg once weekly 1
- Week 17-20: Increase to 12.5 mg once weekly 1
- Week 21+: Increase to 15 mg once weekly (maximum dose) 1
Expected Weight Loss by Dose
- 5 mg weekly: 15.0% weight loss at 72 weeks 1
- 10 mg weekly: 19.5% weight loss at 72 weeks 1
- 15 mg weekly: 20.9% weight loss at 72 weeks (maximum efficacy) 1
- Nearly 40% of patients on 15 mg achieve ≥25% weight loss 1
Administration Technique
Administer as subcutaneous injection into the thigh or abdomen once weekly. 1
Monitoring Requirements
Initial Phase (First 3 Months)
Assess effectiveness and safety at least monthly during the first 3 months. 1
Ongoing Monitoring
- Continue assessment at least quarterly after initial 3 months 1
- Monitor for delayed absorption of oral medications with narrow therapeutic indices 1
- Monitor for cardiac arrhythmias/tachycardia; consider beta blockers if symptomatic 1
Treatment Efficacy Assessment
Evaluate treatment response at 12-16 weeks on the maximum tolerated therapeutic dose (5 mg, 10 mg, or 15 mg). 2 Discontinue tirzepatide if there is less than 4-5% body weight loss at 16 weeks on the maximum tolerated dose, as continuation is unlikely to provide meaningful benefit. 2
Managing Gastrointestinal Side Effects
The most common adverse events are gastrointestinal: nausea (31%), diarrhea (23%), vomiting (12%), and constipation (5%). 2, 3, 4
Management Strategies
- Use slow upward titration schedule as outlined above 1
- Reduce meal size 1
- Limit alcohol and carbonated drinks 1
- Avoid high-fat diets 1
Serious Considerations
- Risk of cholelithiasis and gallstone-related complications 1
- Serious GI events occur more frequently than placebo 4
- Discontinuation due to adverse events is higher with tirzepatide 4
Long-Term Treatment Considerations
Long-term continuous use is necessary to maintain weight loss benefits. Weight regain occurs rapidly upon discontinuation, emphasizing the need for indefinite treatment. 1, 2 Tirzepatide must be used in conjunction with lifestyle modifications for optimal results. 1, 2
Duration of Therapy
There is no established maximum duration for tirzepatide use in weight management, unlike the 2-year lifetime limit for teriparatide (which is a different medication for osteoporosis). 1
Cost Considerations
The average wholesale price is $1,272 per 30-day supply, with national average drug acquisition cost of $1,017 per 30-day supply. 1 Insurance coverage varies significantly and may influence treatment decisions. 1
Comparative Efficacy
Tirzepatide produces 5.5 kg more weight loss than semaglutide 1.0 mg at 40 weeks in head-to-head comparison. 1 The weight loss efficacy is comparable to bariatric surgery outcomes, making it one of the most potent pharmacological options available. 1, 2