What is the appropriate starting dose of tirzepatide (Mounjaro) when switching a patient from weekly 2.4 mg semaglutide (Wegovy) for weight loss?

Converting from Wegovy to Mounjaro: Direct Switching Protocol

When transitioning a patient from semaglutide 2.4 mg weekly (Wegovy) to tirzepatide (Mounjaro), discontinue Wegovy and start tirzepatide at 5 mg weekly the following week, then follow the standard titration schedule regardless of prior semaglutide dose. 1, 2

Why Switch: Efficacy Comparison

Tirzepatide demonstrates superior weight loss compared to semaglutide 2.4 mg, achieving 20.9% total body weight reduction at 72 weeks versus 14.9% with semaglutide—a clinically meaningful 6% absolute difference. 1, 3 In head-to-head comparisons, tirzepatide 15 mg produces an additional 4.23 kg weight loss compared to semaglutide 2.4 mg (95% CI: 3.22–5.25 kg). 4

Beyond weight loss, tirzepatide 15 mg shows statistically significant advantages in multiple cardiometabolic parameters: greater waist circumference reduction, superior triglyceride reduction, and better fasting glucose control compared to semaglutide. 1, 5

Direct Switching Protocol

Week 1: Discontinue Wegovy and Initiate Tirzepatide

• Stop semaglutide 2.4 mg and administer the first dose of tirzepatide 5 mg subcutaneously one week later (on your next scheduled injection day). 1
• The FDA-approved starting dose for tirzepatide is 5 mg weekly, designed to minimize gastrointestinal adverse events while providing therapeutic benefit. 1
• Do not attempt dose equivalency—there is no direct conversion ratio between these medications due to their different mechanisms (tirzepatide is a dual GIP/GLP-1 agonist versus semaglutide's selective GLP-1 action). 1, 6

Weeks 1–16: Standard Titration Schedule

Follow this mandatory escalation protocol to reach therapeutic doses:

• Weeks 1–4: Tirzepatide 5 mg weekly 1
• Weeks 5–8: Increase to 10 mg weekly 1
• Weeks 9+: Increase to 15 mg weekly (maximum dose) 1

Each dose escalation occurs every 4 weeks to minimize gastrointestinal side effects, which are common but typically mild-to-moderate and transient. 1, 6 Slow titration is essential regardless of your prior tolerance to semaglutide 2.4 mg. 1

Concomitant Medication Adjustments

If Taking Insulin

• Reduce basal insulin by 20% when starting tirzepatide to prevent hypoglycemia. 1
• For patients with HbA1c <8%, consider a more aggressive 30% reduction. 1
• Strongly consider discontinuing prandial insulin entirely or reduce each dose by 50%, with plans to discontinue within 2–4 weeks based on glucose monitoring. 1

If Taking Sulfonylureas

• Discontinue sulfonylureas or reduce the dose by 50% before initiating tirzepatide to avoid additive hypoglycemia risk. 1
• Reassess the need for sulfonylurea therapy after approximately 3 months, as tirzepatide frequently achieves adequate glycemic control independently. 1

If Taking DPP-4 Inhibitors

• Stop all DPP-4 inhibitors (sitagliptin, linagliptin, etc.) before starting tirzepatide—concurrent use provides no additional benefit. 1

Monitoring During Transition

Weeks 1–4 (Initial Transition)

• Assess every 4 weeks for gastrointestinal tolerance (nausea, vomiting, diarrhea), weight loss progress, and blood pressure. 1
• Check fasting glucose daily before breakfast for the first 2 weeks if on insulin or sulfonylureas. 1
• If any glucose reading <70 mg/dL, immediately reduce insulin further by 10–20%. 1

Weeks 12–16 (Efficacy Assessment)

• Evaluate treatment response at 12–16 weeks on the maximum tolerated therapeutic dose. 1
• Discontinue if weight loss is <5% after 3 months at therapeutic dose, indicating inadequate response. 1

Ongoing (Every 3 Months)

• Monitor weight, blood pressure, cardiovascular risk factors, and medication adherence. 1
• Assess for signs of pancreatitis (persistent severe abdominal pain) and gallbladder disease. 1

Safety Profile and Adverse Effects

Both medications share similar adverse effect profiles, with gastrointestinal effects predominating: nausea (17–22% with tirzepatide vs. 18–40% with semaglutide), diarrhea (13–16% vs. 12%), and vomiting (6–10% vs. 8–16%). 1, 6 These symptoms are typically mild-to-moderate, occur primarily during dose escalation, and decrease over time. 1, 6

Serious but rare risks include pancreatitis and gallbladder disease (cholelithiasis, cholecystitis), though causality has not been definitively established. 1 Both medications carry identical contraindications: personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN 2). 1

When NOT to Switch

Do not switch if the patient has:

• Established cardiovascular disease without diabetes—semaglutide 2.4 mg is the only obesity medication with proven cardiovascular benefit, reducing cardiovascular death, nonfatal MI, or stroke by 20% (HR 0.80). 1
• Recent heart failure decompensation—avoid GLP-1 receptor agonists in this setting. 1
• Severe gastroparesis or clinically meaningful GI motility disorders—tirzepatide may worsen symptoms. 1

Expected Outcomes After Switching

• Weight loss magnitude: Expect approximately 20.9% total body weight loss at 72 weeks with tirzepatide 15 mg, compared to the 14.9% you would have achieved continuing semaglutide. 1, 3
• Cardiometabolic improvements: Greater reductions in waist circumference, triglycerides, and fasting glucose compared to semaglutide. 1, 5
• Glycemic control: If diabetic, expect HbA1c reductions of 1.87–2.59% with tirzepatide versus 1.4–1.48% with semaglutide. 1, 6

Critical Implementation Pitfalls to Avoid

• Do not attempt to "match" doses—always start tirzepatide at 5 mg weekly regardless of prior semaglutide dose. 1
• Do not skip the titration schedule—rapid escalation markedly increases gastrointestinal adverse events and discontinuation rates. 1
• Do not forget to reduce insulin or sulfonylureas—the combination significantly raises hypoglycemia risk. 1
• Do not combine with other GLP-1 receptor agonists—this is pharmacologically redundant and potentially harmful. 1
• Do not assume cardiovascular protection transfers—tirzepatide has not demonstrated the same cardiovascular outcome benefits as semaglutide in patients with established CVD. 1

Cost Considerations

The average wholesale price for tirzepatide is approximately $1,272 per 30-day supply, compared to $1,619 for semaglutide 2.4 mg. 1 Insurance authorization may be challenging, particularly for obesity management without diabetes. 1 Lifelong treatment is typically necessary to maintain weight loss and metabolic benefits—sudden discontinuation results in regain of one-half to two-thirds of lost weight within 1 year. 1