What is the recommended dosage of tirzepatide (Zepbound) for an adult patient with a history of obesity or type 2 diabetes transitioning from semaglutide (Wegovy) 2.4mg?

Transitioning from Wegovy 2.4mg to Zepbound: Recommended Starting Dose

When transitioning from semaglutide (Wegovy) 2.4mg weekly to tirzepatide (Zepbound), start with tirzepatide 5mg weekly—the FDA-approved starting dose—regardless of your prior semaglutide dose. 1

Direct Switching Protocol

• Discontinue Wegovy and begin Zepbound 5mg weekly the following week 1
• Do not attempt to "match" doses between medications, as they have different mechanisms of action and potency profiles 1
• The standard tirzepatide titration schedule must be followed to minimize gastrointestinal adverse effects, even though you were previously on maximum-dose semaglutide 1

Tirzepatide Titration Schedule After Transition

Follow this escalation schedule, increasing every 4 weeks based on tolerance 1:

• Weeks 1-4: 5mg weekly
• Weeks 5-8: 7.5mg weekly
• Weeks 9-12: 10mg weekly
• Weeks 13-16: 12.5mg weekly
• Week 17+: 15mg weekly (maximum maintenance dose)

The gradual titration is essential because tirzepatide's dual GIP/GLP-1 receptor mechanism produces different gastrointestinal effects than semaglutide's single GLP-1 action, despite your prior tolerance to Wegovy 1

Why Tirzepatide May Be Superior for Your Goals

Tirzepatide demonstrates superior weight loss compared to semaglutide 2.4mg, achieving 20.9% total body weight loss versus 14.9% with semaglutide at 72 weeks 1, 2. This represents an additional 6% absolute weight loss advantage 1. In direct comparison trials, tirzepatide 15mg produced 6.5 percentage points greater weight loss than semaglutide 2.4mg 2.

Beyond weight loss, tirzepatide 15mg provides statistically significant advantages over semaglutide including 1:

• Greater waist circumference reduction
• Superior triglyceride reduction
• Better fasting glucose control
• Improved cardiometabolic risk factors

Critical Safety Considerations

Absolute Contraindications

Do not use tirzepatide if you have 1:

• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2 (MEN2)

Expected Side Effects During Transition

Anticipate gastrointestinal effects even though you tolerated Wegovy, as tirzepatide's dual mechanism affects the GI system differently 1, 3:

• Nausea: 17-22% of patients 1
• Diarrhea: 13-16% of patients 1
• Vomiting: 6-10% of patients 1

These effects are typically mild-to-moderate, occur primarily during dose escalation, and decrease over time 1, 3

Medication Adjustments Required

If you're taking concomitant medications 1:

• Insulin: Reduce basal insulin by 20% when starting tirzepatide to prevent hypoglycemia
• Sulfonylureas: Discontinue or reduce dose by 50%
• Other GLP-1 agonists: Must be completely discontinued—never combine tirzepatide with semaglutide or other GLP-1 receptor agonists 1

Monitoring Schedule After Transition

• Weeks 0-16 (titration phase): Evaluate every 4 weeks for gastrointestinal tolerance, weight loss progress, blood pressure, and signs of pancreatitis or gallbladder disease 1
• After week 16 (maintenance): Assess at least every 3 months for weight stability, cardiovascular risk factors, and medication adherence 1

Important Caveats About Long-Term Use

Tirzepatide requires lifelong treatment to maintain weight loss benefits—discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 1. The medication must be combined with a reduced-calorie diet (500-kcal deficit) and minimum 150 minutes per week of physical activity for optimal results 1.

When Tirzepatide May Not Be the Right Choice

Consider remaining on semaglutide 2.4mg instead if you have 1:

• Established cardiovascular disease: Semaglutide has proven cardiovascular outcome benefits with a 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80), while tirzepatide's cardiovascular outcomes data is still emerging
• Cost constraints: Average wholesale price is $1,272 per 30-day supply for tirzepatide versus $1,557 for semaglutide, though insurance authorization may be more challenging for tirzepatide 1

Expected Timeline for Results

Evaluate treatment response at 12-16 weeks on your maximum tolerated dose 1. If you achieve less than 5% weight loss after 3 months at therapeutic dose, consider alternative approaches or treatment intensification 1.