What is the recommended dose of tirzepatide (glucagon-like peptide-1 (GLP-1) receptor agonist) for weight loss?

Recommended Dosing of Tirzepatide for Weight Loss

For weight loss in non-diabetic adults, tirzepatide should be initiated at a low dose and gradually titrated to 15 mg once weekly, which provides the maximum weight loss benefit of 20.9% at 72 weeks. 1

Dosing Algorithm

• Start with a low dose and gradually titrate upward to minimize gastrointestinal side effects 2
• Initial dose: Begin with 2.5 mg subcutaneously once weekly for 4 weeks 2
• Titration schedule:
  • Increase to 5 mg once weekly for 4 weeks 1
  • Increase to 7.5 mg once weekly for 4 weeks 1
  • Increase to 10 mg once weekly for 4 weeks 1
  • Increase to 12.5 mg once weekly for 4 weeks 1
  • Increase to maximum dose of 15 mg once weekly 1

Efficacy 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
• Placebo (with lifestyle modifications): 3.1% weight loss 1

Patient Selection Criteria

• FDA approved 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) 2
• Tirzepatide was approved for obesity treatment in November 2023 1

Monitoring Recommendations

• Assess effectiveness and safety at least monthly for the first 3 months 1
• Continue monitoring at least quarterly thereafter 1
• Monitor for potential consequences of delayed absorption of oral medications with narrow therapeutic indices 1, 2
• Monitor for gastrointestinal side effects, which are most common during dose escalation 1, 2

Managing Side Effects

• Gastrointestinal side effects are most common (nausea, vomiting, diarrhea, constipation) 1, 2
• Management strategies:
  • Slow upward titration schedule 1, 2
  • Reduce meal size 1
  • Limit alcohol and carbonated drinks 1
  • Avoid high-fat diets 1

Contraindications

• Personal or family history of medullary thyroid carcinoma 1, 2
• Multiple Endocrine Neoplasia syndrome type 2 1, 2
• Severe gastrointestinal disease including gastroparesis 2

Clinical Pearls

• Tirzepatide is a dual GIP/GLP-1 receptor co-agonist that provides greater weight loss than selective GLP-1 receptor agonists 3, 4
• In clinical trials, many patients (up to 68.4%) lost more than 10% of baseline body weight 3, 5
• Maximum weight loss in clinical trials was 22.5% of body weight 6, 5
• Long-term use is necessary to maintain weight loss benefits 1
• Tirzepatide also improves multiple cardiometabolic risk factors including blood pressure 2, 4
• The medication must be used in conjunction with lifestyle modifications for optimal results 1

Cost Considerations

• Average Wholesale Price (AWP): $1,272 for a 30-day supply (all doses) 1
• National Average Drug Acquisition Cost (NADAC): $1,017 for a 30-day supply 1
• Insurance coverage varies and may influence treatment decisions 1