What are the treatment options with Monjaro (tirzepatide) and Ozempic (semaglutide) for an adult patient with a body mass index (BMI) of 30 or higher, or 27 or higher with comorbidities such as diabetes or heart disease, seeking weight loss?

Monjaro and Ozempic for Weight Loss

Both Monjaro (tirzepatide) and Ozempic (semaglutide) are highly effective for weight loss in adults with obesity, but tirzepatide demonstrates superior efficacy with 20.9% weight loss compared to semaglutide's 14.9% at therapeutic doses, making tirzepatide the preferred first-line choice when maximum weight loss is the primary goal. 1, 2

Patient Eligibility Criteria

You should prescribe these medications for patients with:

• BMI ≥30 kg/m² without additional risk factors, OR 3
• BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, cardiovascular disease) 3, 1

Critical caveat: These medications must be combined with lifestyle interventions—never prescribe as monotherapy. 1 The FDA approval criteria require concurrent reduced-calorie diet and increased physical activity. 1

Medication Selection Algorithm

First-Line Choice: Tirzepatide (Monjaro)

Prioritize tirzepatide 15mg weekly when maximum weight loss is the primary goal. 1, 2 Tirzepatide achieves 20.9% weight loss at 72 weeks versus semaglutide's 14.9%. 1, 2 The dual GIP/GLP-1 receptor mechanism provides superior metabolic benefits including greater waist circumference reduction, better triglyceride control, and improved fasting glucose. 1

Dosing schedule for tirzepatide: 1

• Start at 5mg weekly subcutaneously
• Titrate upward every 4 weeks based on tolerance
• Maximum dose: 15mg weekly

Second-Line Choice: Semaglutide 2.4mg (Wegovy, NOT Ozempic)

Use semaglutide 2.4mg weekly if tirzepatide is unavailable, not tolerated, or if the patient has established cardiovascular disease. 1, 2 Semaglutide has proven cardiovascular benefit with a 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80). 1, 2

Important distinction: Ozempic (semaglutide 1.0mg) is FDA-approved only for type 2 diabetes, not obesity. 2 Wegovy (semaglutide 2.4mg) is the FDA-approved formulation for weight loss. 2

Dosing schedule for semaglutide 2.4mg: 1

• Week 1-4: 0.25mg weekly
• Week 5-8: 0.5mg weekly
• Week 9-12: 1.0mg weekly
• Week 13-16: 1.7mg weekly
• Week 17+: 2.4mg weekly (maintenance)

Expected Weight Loss Outcomes

Tirzepatide: 15-21% weight loss achievable at higher doses over 72 weeks 1

Semaglutide 2.4mg: 14.9-17.4% weight loss in non-diabetic patients with obesity over 68 weeks 2

Weight loss is consistently greater in non-diabetic patients (6.1-17.4%) compared to those with diabetes (4-6.2%). 2

Mandatory Lifestyle Modifications

Combine pharmacotherapy with: 1

• Caloric deficit of 500-kcal reduction below daily requirements
• Minimum 150 minutes/week of physical activity
• Resistance training to preserve lean body mass (critical to prevent muscle loss)

Monitoring Schedule

During titration (first 16 weeks): 1

• Assess every 4 weeks for gastrointestinal tolerance, weight loss progress, and blood pressure

After reaching maintenance dose: 1

• Monitor at least every 3 months for weight, blood pressure, cardiovascular risk factors
• Evaluate efficacy at 12-16 weeks on maximum tolerated dose

Discontinue medication if <5% weight loss achieved after 12 weeks at maintenance dose—this predicts poor long-term response. 1

Safety Profile and Adverse Effects

Common gastrointestinal effects (occur in majority of patients): 1, 2

• Nausea (17-44% of patients)
• Diarrhea (12-32%)
• Vomiting (7-25%)
• Constipation (10-23%)

These are typically mild-to-moderate, transient, and decrease over time. 1, 2 Slow titration minimizes these effects. 1

Serious but rare risks: 1, 2

• Pancreatitis (monitor for persistent severe abdominal pain)
• Gallbladder disease (cholelithiasis, cholecystitis)
• Acute kidney injury

Absolute contraindications for both medications: 1, 2

• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2

Cardiovascular Benefits Beyond Weight Loss

Semaglutide 2.4mg reduces cardiovascular events by 20% (HR 0.80) in patients with obesity and established cardiovascular disease. 1, 2 This makes it particularly valuable for patients with pre-existing cardiovascular disease. 1

Both medications improve: 1

• Blood pressure (may require antihypertensive adjustment)
• Lipid profiles
• Insulin sensitivity
• Liver fat (significant decreases in hepatic steatosis)

Critical Pitfalls to Avoid

Never prescribe as monotherapy—must be combined with lifestyle modification throughout treatment. 1 This is an FDA approval requirement and maximizes efficacy. 1

Do not continue ineffective treatment beyond 12 weeks at maintenance dose if <5% weight loss achieved—switch to alternative medication instead. 1

These medications require lifelong use—sudden discontinuation results in regain of one-half to two-thirds of lost weight within 1 year. 1, 2 Counsel patients upfront about the need for long-term treatment. 2

For patients on oral contraceptives starting tirzepatide: Switch to non-oral methods or add barrier contraception for 4 weeks after initiation and each dose escalation. 1

Special Population Considerations

Patients with type 2 diabetes: Both medications offer dual benefits of weight loss and improved glycemic control. 1, 2 Prioritize tirzepatide or semaglutide 2.4mg over lower-dose semaglutide due to greater HbA1c reduction. 1

Patients with cardiovascular disease: Semaglutide 2.4mg has proven cardiovascular benefit and should be prioritized. 1, 2

Patients with hypothyroidism: Both medications are generally safe, though monitoring of thyroid function is recommended. 1 Ensure thyroid function is optimized before starting treatment. 1

Cost Considerations

Average wholesale prices: 2

• Tirzepatide: approximately $1,272 per 30-day supply
• Semaglutide 2.4mg: approximately $1,600 per 30-day supply

Insurance authorization may be challenging, particularly for obesity management without diabetes. 1 Document failed lifestyle modifications for both clinical appropriateness and insurance authorization. 1