Zepbound (Tirzepatide) Indication
Zepbound (tirzepatide) is FDA-approved 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, as an adjunct to reduced calorie diet and increased physical activity.
Mechanism of Action
Tirzepatide is a first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works through multiple mechanisms:
- Activates both GIP and GLP-1 receptors to enhance weight loss effects
- Reduces appetite and food intake through central nervous system pathways
- Slows gastric emptying, promoting satiety
- Improves insulin sensitivity and glucose metabolism
Clinical Efficacy for Weight Management
Tirzepatide demonstrates superior weight reduction compared to other medications:
- Produces mean weight reduction of 8.47 kg compared to usual care 1
- Enables 3-67% of patients to achieve ≥10% weight reduction from baseline 1
- Significantly outperforms selective GLP-1 receptor agonists like semaglutide for weight loss 2, 3
- Demonstrates dose-dependent efficacy with greater effects at higher doses (5mg, 10mg, 15mg) 4, 5
Dosing and Administration
- Starting dose: 2.5 mg subcutaneously once weekly for 4 weeks
- Gradual titration: Increase to 5 mg, then 10 mg, and finally 15 mg once weekly as tolerated and needed for optimal weight management 2
- No dose adjustment needed for mild to moderate renal impairment, but caution advised with severe renal impairment (eGFR <30 mL/min/1.73m²) 2
Safety Considerations
The safety profile is generally similar to other GLP-1 receptor agonists:
- Most common adverse effects are gastrointestinal (nausea, vomiting, diarrhea, constipation) 6, 4
- Low risk of hypoglycemia when used without insulin or insulin secretagogues 1, 3
- Tirzepatide probably reduces severe hypoglycemia compared to insulin (RR: 0.21 [CI: 0.11 to 0.38]) 1
Important Contraindications
- Personal or family history of medullary thyroid cancer
- Multiple endocrine neoplasia syndrome type 2
- Pregnancy or breastfeeding
- Severe gastroparesis 2
Monitoring Recommendations
- Regular monitoring of weight, gastrointestinal symptoms, and renal function
- Comprehensive eye examination before initiating therapy and regular follow-up
- Blood pressure monitoring due to potential cardiovascular effects 2
Clinical Pearls
- Slow dose titration improves gastrointestinal tolerability
- Recommend smaller meal sizes and avoiding high-fat meals to reduce GI side effects
- Tirzepatide is distinct from Mounjaro, which is the same molecule (tirzepatide) but indicated specifically for type 2 diabetes management
- The exceptional weight loss efficacy makes it particularly valuable for patients with obesity-related complications
While tirzepatide is also approved as Mounjaro for type 2 diabetes management, Zepbound is specifically indicated for weight management in adults with obesity or overweight with weight-related comorbidities.