What is the equivalent dose of Zepbound (tirzepatide) for a patient taking Wegovy (semaglutide) 2.4 mg per week?

Switching from Wegovy 2.4 mg to Equivalent Zepbound Dose

When switching from Wegovy (semaglutide) 2.4 mg weekly to Zepbound (tirzepatide), the recommended starting dose is 5 mg of Zepbound weekly, with potential titration to higher doses as tolerated.

Rationale for Dose Selection

Tirzepatide (Zepbound) is a dual GIP/GLP-1 receptor agonist that has shown superior efficacy compared to semaglutide (Wegovy) in clinical trials:

• Tirzepatide has demonstrated greater efficacy in both glycemic control and weight reduction compared to semaglutide at equivalent doses 1
• In the SURPASS-2 trial, tirzepatide at all doses (5 mg, 10 mg, and 15 mg) was superior to semaglutide 1 mg for glycemic control 1
• Weight reductions were significantly greater with tirzepatide than with semaglutide (additional weight loss of 1.9 kg with 5 mg, 3.6 kg with 10 mg, and 5.5 kg with 15 mg compared to semaglutide) 1

Switching Protocol

1. Initial dose: Start with tirzepatide 5 mg weekly

   • This is the recommended starting dose when switching directly from a GLP-1 receptor agonist 2
   • No need for dose titration from lower doses when switching from a stable GLP-1 RA regimen

2. Monitoring period: Evaluate response for 4-12 weeks

   • Real-world evidence shows improved glycemic outcomes and additional weight reduction when switching from GLP-1 RAs to tirzepatide 5 mg 2
   • Mean HbA1c reduction of 0.43% and weight reduction of 2.15 kg over 12 weeks have been observed when switching from GLP-1 RAs to tirzepatide 5 mg 2

3. Dose titration: Consider increasing to 10 mg after 4 weeks, then to 15 mg after another 4 weeks if needed and tolerated

   • Titration should be based on clinical response and tolerability
   • The maximum dose of tirzepatide is 15 mg weekly

Gastrointestinal Side Effect Management

Gastrointestinal side effects are common with both medications but may occur when switching:

• Approximately 13.2% of patients develop gastrointestinal events when switching from GLP-1 RAs to tirzepatide 5 mg 2
• Only 2% of patients discontinue tirzepatide due to adverse events when switching from GLP-1 RAs 2

To minimize side effects:

• Take smaller meal sizes
• Avoid high-fat foods
• Limit alcohol and carbonated beverages
• Moderate carbohydrate intake

Clinical Considerations

1. Efficacy comparison: Tirzepatide has shown greater efficacy than semaglutide for both weight loss and glycemic control

   • Tirzepatide reduced the risk of major adverse cardiovascular events compared with semaglutide (HR 0.86; 95% CI, 0.74-0.99) 3
   • Tirzepatide demonstrated superior weight loss compared to semaglutide in clinical trials 1

2. Renal function: No dose adjustment is required for either medication if eGFR is ≥30 mL/min/1.73m² 4

3. Perioperative considerations: Both medications have similar pharmacokinetic profiles with long half-lives (tirzepatide: 5 days; semaglutide: 7 days) 5

   • Consider timing of elective procedures relative to dosing schedule

Important Caveats

• Patients may experience transient worsening of glycemic control during the switch
• Both medications have similar contraindications (personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2) 4
• The switch should be made with the understanding that tirzepatide may cause additional weight loss beyond what was achieved with semaglutide 2

This approach provides a straightforward transition from Wegovy to Zepbound while maximizing efficacy and minimizing side effects based on the most recent clinical evidence.