Criteria for Zepbound (Tirzepatide)
Zepbound is FDA-approved for two specific indications: (1) weight reduction and long-term weight maintenance in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity, and (2) treatment of moderate to severe obstructive sleep apnea in adults with obesity—both used in combination with a reduced-calorie diet and increased physical activity. 1
Primary Indications
Weight Management Criteria
- BMI ≥30 kg/m² (obesity) OR BMI ≥27 kg/m² (overweight) with at least one weight-related comorbid condition 1
- Weight-related comorbidities include hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease 1
- Must be combined with reduced-calorie diet and increased physical activity 1
Obstructive Sleep Apnea Criteria
- Moderate to severe OSA in adults with obesity 1
- Clinical trial populations included 7% with baseline OSA 1
Absolute Contraindications
Do not use Zepbound in patients with:
- Personal or family history of medullary thyroid carcinoma (MTC) 1
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
- History of suicidal attempts or active suicidal ideation 1
- Pregnancy (due to risk of thyroid C-cell tumors and weight loss risks) 1
Important Limitations and Warnings
Coadministration Restrictions
- Do not combine with other tirzepatide-containing products or any GLP-1 receptor agonist 1
High-Risk Populations Requiring Caution
- Patients with diabetic retinopathy should be monitored for progression 1
- Patients on concomitant antihypertensive therapy have higher risk of hypotension (2.2% vs 1.0% without antihypertensives) 1
- Patients with history of pancreatitis require careful consideration due to acute pancreatitis risk 1
- Patients with severe gastrointestinal disease should be evaluated carefully, as 56% experience GI adverse reactions 1
Surgical Considerations
- Inform all healthcare providers prior to any planned surgeries or procedures due to delayed gastric emptying and pulmonary aspiration risk during general anesthesia 1
Clinical Trial Population Characteristics
The FDA approval was based on trials with the following baseline characteristics 1:
- Mean age: 47 years
- Mean BMI: 37.4 kg/m²
- 29% had BMI ≥40 kg/m²
- 41% had hypertension
- 37% had dyslipidemia
- 25% had type 2 diabetes mellitus
- 7% had obstructive sleep apnea
- 4% had cardiovascular disease
Monitoring Requirements
Before Initiating Treatment
- Screen for personal/family history of MTC or MEN 2 1
- Assess for history of suicidal ideation or attempts 1
- Document baseline weight and BMI 1
- Evaluate for diabetic retinopathy if diabetes present 1
During Treatment
- Monitor for suicidal thoughts or behaviors, particularly emergence or worsening of depression or unusual mood changes; discontinue immediately if these occur 1
- Monitor for gastrointestinal symptoms, especially during dose escalation in first 20 weeks 1
- Assess blood pressure regularly, particularly in patients on antihypertensive medications 1
- Watch for signs of acute pancreatitis (persistent severe abdominal pain) 1
- Monitor for hypoglycemia if patient is on other glucose-lowering medications 1
Common Adverse Reactions Leading to Discontinuation
4.8% to 6.7% of patients discontinued due to adverse reactions (vs 3.4% with placebo), with the majority discontinuing in the first few months due to gastrointestinal reactions 1:
- Nausea (25-28% vs 8% placebo)
- Diarrhea (19-23% vs 8% placebo)
- Vomiting (8-13% vs 2% placebo)
- Constipation (11-17% vs 5% placebo)
Special Clinical Contexts
Type 1 Diabetes
- Not FDA-approved for type 1 diabetes 1
- Observational data suggests potential efficacy but requires randomized controlled trials 2