What is the best approach to transition a patient with inadequate glycemic control from Ozempic (semaglutide) 1 mg subcutaneously (SC) to Mounjaro (tirzepatide)?

Transitioning from Ozempic 1 mg to Mounjaro

Stop Ozempic and start Mounjaro at 2.5 mg subcutaneously once weekly the following week, then titrate up every 4 weeks to the maintenance dose of 5 mg, with further escalation to 10 mg or 15 mg based on glycemic response and tolerability. 1

Direct Transition Protocol

• Discontinue Ozempic 1 mg immediately and wait approximately 1 week (one dosing interval) before initiating Mounjaro to allow for washout, though both medications can be started without a mandatory washout period given their similar mechanisms 2

• Start Mounjaro at 2.5 mg subcutaneously once weekly as the initial dose, regardless of prior semaglutide dose—this is the FDA-mandated starting dose to minimize gastrointestinal side effects 2

• Titrate Mounjaro every 4 weeks following this schedule:

  • Weeks 1-4: 2.5 mg once weekly
  • Weeks 5-8: 5 mg once weekly (first maintenance dose)
  • Weeks 9-12: 10 mg once weekly (if additional glycemic control needed)
  • Weeks 13+: 15 mg once weekly (maximum dose for optimal efficacy) 1

Expected Outcomes and Comparative Efficacy

• Tirzepatide demonstrates superior glycemic control compared to semaglutide 1 mg, with HbA1c reductions of approximately 1.84% with tirzepatide 10 mg and 1.96% with tirzepatide 15 mg, versus 1.39% with semaglutide 1 mg 1

• Greater weight loss occurs with tirzepatide, with mean reductions of 9.57 kg (tirzepatide 15 mg) to 7.24 kg (tirzepatide 10 mg) compared to 4.44 kg with semaglutide 1 mg 1

• Real-world data confirms these benefits, showing 16.5% body weight loss with tirzepatide versus 14.1% with semaglutide 2.4 mg after 1 year 3

Managing Gastrointestinal Side Effects During Transition

• Nausea and vomiting are the most common side effects during dose escalation, occurring more frequently with higher tirzepatide doses but typically self-limited 2, 1

• Counsel patients to eat smaller portions, use mindful eating practices (stop when full), and decrease intake of high-fat or spicy foods to mitigate GI symptoms 2

• Consider slower dose titration (extending the 4-week intervals to 6-8 weeks) in patients experiencing significant GI challenges, though this is not standard protocol 2

• Do not administer tirzepatide with DPP-4 inhibitors as both work through incretin pathways and are not approved for concurrent use 2

Monitoring Requirements

• Check HbA1c every 3 months during titration to assess glycemic response and guide dose escalation decisions 2

• Monitor for diabetic retinopathy complications in patients with prior proliferative retinopathy, as rapid glucose reduction (more pronounced with tirzepatide) may transiently worsen retinopathy 2

• Ensure recent eye examination prior to initiating tirzepatide in high-risk patients (those with diabetes duration ≥10 years or existing retinopathy) 2

• Assess for biliary disease if patients develop right upper quadrant pain, as both GLP-1 RAs and dual GIP/GLP-1 RAs increase risk of cholelithiasis and cholecystitis 2

Critical Pitfalls to Avoid

• Never start tirzepatide at doses higher than 2.5 mg, even though the patient was on semaglutide 1 mg—the initial 2.5 mg dose is mandatory for tolerability regardless of prior GLP-1 RA exposure 2

• Do not discontinue metformin when transitioning between these agents unless contraindicated (eGFR <30 mL/min/1.73 m²), as metformin provides complementary glucose-lowering effects 2

• Avoid use in patients with gastroparesis or history of severe GI dysmotility, as tirzepatide significantly delays gastric emptying 2

• Discontinue 3-4 days before scheduled surgery to reduce risk of aspiration and allow for normalization of gastric emptying 2

• Do not use tirzepatide in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, as thyroid C-cell tumors were identified in rodent studies 2

Renal Considerations

• No dose adjustment required for tirzepatide across all levels of kidney function, including dialysis, though glucose-lowering efficacy diminishes at eGFR <45 mL/min/1.73 m² 2

• Continue tirzepatide for cardiovascular and potential renal benefits even when eGFR falls below 45 mL/min/1.73 m², similar to SGLT2 inhibitor guidance 2

When to Escalate Beyond 5 mg

• Advance to 10 mg if HbA1c remains >7% after 4 weeks on tirzepatide 5 mg, or if additional weight loss is desired 1

• Escalate to 15 mg for maximum efficacy when HbA1c targets are not met with 10 mg, as this dose provides the greatest HbA1c reduction (-1.96%) and weight loss (-9.57 kg) compared to placebo 1

• Most patients require 10-15 mg for optimal outcomes, as only 25.9% of real-world patients remained on lower doses, with the majority requiring dose escalation for adequate glycemic control 3