What is the recommended approach for converting a patient from Ozempic (semaglutide) to Zepbound (tirzepatide)?

Converting from Ozempic (Semaglutide) to Zepbound (Tirzepatide)

There is no established conversion protocol between semaglutide and tirzepatide—you should start tirzepatide at the initial 2.5 mg dose regardless of the patient's current semaglutide dose, following standard titration protocols. 1

Discontinuation and Initiation Strategy

Stop semaglutide and begin tirzepatide at 2.5 mg subcutaneously once weekly. The 2.5 mg starting dose is specifically designed to minimize gastrointestinal side effects and is not a therapeutic dose—it serves as a tolerability primer. 1

• No dose equivalency exists between these medications despite both being incretin-based therapies. 2, 3
• The dual GIP/GLP-1 receptor agonist mechanism of tirzepatide differs fundamentally from semaglutide's selective GLP-1 receptor agonism, producing distinct pharmacodynamic effects on insulin secretion, insulin sensitivity, and glucagon suppression. 4

Standard Titration Protocol

Escalate tirzepatide by 2.5 mg every 4 weeks until reaching the target maintenance dose of 5 mg, 10 mg, or 15 mg based on efficacy and tolerability. 1

• Week 0-4: 2.5 mg once weekly
• Week 4-8: 5 mg once weekly
• Week 8-12: 7.5 mg once weekly
• Week 12-16: 10 mg once weekly
• Week 16+: 12.5 mg once weekly
• Week 20+: 15 mg once weekly (if needed)

The 15 mg dose provides maximum efficacy with 20.9% weight loss at 72 weeks compared to 15.0% with 5 mg. 1

Monitoring During Conversion

Assess effectiveness and safety at least monthly for the first 3 months during dose escalation. 1

• Monitor blood glucose closely, particularly in the first 2-4 weeks, as tirzepatide produces greater glycemic reductions than semaglutide (HbA1c reduction of -2.30% with tirzepatide 15 mg vs -1.86% with semaglutide 1 mg). 2
• Reduce insulin or sulfonylurea doses by 20-30% at conversion to minimize hypoglycemia risk, as tirzepatide demonstrates superior glucose-lowering compared to semaglutide. 5, 2
• Evaluate treatment efficacy at 12-16 weeks on the maximum tolerated dose; consider discontinuation if less than 4-5% body weight loss at 16 weeks. 1

Managing Gastrointestinal Side Effects

Expect similar or slightly higher rates of GI adverse events compared to semaglutide, particularly nausea (17-22% with tirzepatide vs 18% with semaglutide), diarrhea (13-16% vs 12%), and vomiting (6-10% vs 8%). 2

• The gradual titration schedule specifically mitigates these effects—do not accelerate dose escalation even if the patient tolerated high-dose semaglutide well. 5, 1
• Counsel patients to eat smaller portions and that nausea is typically self-limited with longer-acting agents. 5
• If more than 2 consecutive doses are missed, resume at the same dose if previously well-tolerated; otherwise lower the next dose. If 3+ consecutive doses are missed, restart the titration schedule. 5, 1

Special Considerations

For patients on oral contraceptives: Advise non-oral contraception or addition of a non-oral method for 4 weeks after each dose escalation, as tirzepatide may delay gastric emptying and affect oral medication absorption. 1

For patients with diabetic retinopathy: Exercise particular caution, as semaglutide has been associated with diabetic retinopathy complications related to rapid glucose reductions. 5 Ensure recent ophthalmologic examination before conversion, as tirzepatide produces even more pronounced glycemic improvements. 2, 4

Contraindications remain the same: Personal or family history of medullary thyroid cancer, MEN2 syndrome, and history of serious hypersensitivity reactions. 5

Expected Outcomes

Tirzepatide produces superior weight loss and glycemic control compared to semaglutide. 2, 3, 6

• Weight reduction: Tirzepatide 15 mg achieves mean weight loss of 9.57 kg vs 4.97 kg with semaglutide 2.0 mg compared to placebo. 3
• HbA1c reduction: Tirzepatide 15 mg reduces HbA1c by -2.30% vs -1.86% with semaglutide 1 mg. 2
• In patients with T2D and obesity, tirzepatide 15 mg produces 20.2% weight reduction vs 13.7% with semaglutide at 72 weeks. 7

Medication Interactions

Do not combine tirzepatide with other GLP-1 receptor agonists or DPP-4 inhibitors, as they work through overlapping GLP-1 signaling pathways and are not approved for concurrent use. 5

Monitor medications with narrow therapeutic indices (e.g., warfarin) closely during titration due to potential delayed absorption from gastric emptying effects. 1