At what Body Mass Index (BMI) is Zepbound (tirzepatide) recommended in the absence of prediabetes?

BMI Requirements for Zepbound (Tirzepatide) Without Prediabetes

Zepbound (tirzepatide) is recommended for individuals with a BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity, even in the absence of prediabetes. 1

FDA Approval and Indications

• Tirzepatide (Zepbound) received FDA approval in November 2023 for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbid condition 1
• Weight-related comorbidities can include hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, and others, but do not require the presence of prediabetes 1
• Tirzepatide is a dual GIP/GLP-1 receptor co-agonist administered subcutaneously once weekly 1, 2

Efficacy for Weight Management

• Tirzepatide demonstrates superior weight loss compared to other weight management medications:
  • 5 mg weekly: 15.0% weight loss at 72 weeks
  • 10 mg weekly: 19.5% weight loss
  • 15 mg weekly: 20.9% weight loss (maximum efficacy) 1, 3
• In clinical trials, 91% of participants achieved ≥5% weight loss, and 57% achieved ≥20% weight loss with the 15 mg dose 3
• Tirzepatide shows greater weight reduction (20.9%) compared to semaglutide (14.9%) in clinical trials 4, 3

Dosing and Administration

• Recommended starting with a low dose and gradually titrating upward:
  • Start with lower doses and increase to 5 mg once weekly for 4 weeks
  • Then gradually increase to 7.5 mg, 10 mg, 12.5 mg, and finally to the maximum dose of 15 mg once weekly 1
• Slow titration helps minimize gastrointestinal side effects 1

Monitoring and Evaluation

• Assess effectiveness and safety at least monthly for the first 3 months, and at least quarterly thereafter 1, 5
• If a patient's response is <5% weight loss after 3 months or if there are significant safety or tolerability issues, consider discontinuing the medication and exploring alternative approaches 5
• Monitor for potential consequences of delayed absorption of oral medications 1

Side Effects and Contraindications

• Most common adverse events are gastrointestinal, including nausea, vomiting, diarrhea, and constipation 1, 3
• Management strategies for GI side effects include:
  • Slow upward titration schedule
  • Reducing meal size
  • Limiting alcohol and carbonated drinks
  • Avoiding high-fat diets 1
• Contraindicated in patients with:
  • Personal or family history of medullary thyroid carcinoma
  • Multiple Endocrine Neoplasia syndrome type 2
  • Severe gastrointestinal disease including gastroparesis 1
• Not recommended during pregnancy or for individuals trying to conceive 5

Long-term Considerations

• Long-term use is necessary to maintain weight loss benefits, as weight regain typically occurs after discontinuation 1
• The medication must be used in conjunction with lifestyle modifications (diet, physical activity, behavioral changes) for optimal results 1, 5
• Consider cost implications, as the average wholesale price is approximately $1,272 for a 30-day supply 1

Clinical Pearls

• Tirzepatide improves multiple cardiometabolic risk factors beyond weight loss, including blood pressure and lipid profiles 1, 3
• For patients not reaching treatment goals, consider intensifying treatment with additional approaches (e.g., metabolic surgery, additional pharmacologic agents, structured lifestyle management programs) 4
• When selecting between weight management medications, tirzepatide may be preferred for patients seeking maximum weight loss potential 4, 3