Can a 62‑year‑old woman on dulaglutide (Trulicity) 4.5 mg weekly for two years start tirzepatide (Mounjaro) at 5 mg directly, or must she titrate the dose?

Direct Transition from Trulicity 4.5mg to Mounjaro 5mg

A 62-year-old woman on dulaglutide (Trulicity) 4.5 mg weekly for two years can start tirzepatide (Mounjaro) at 5 mg weekly directly without titration, as the FDA-approved starting dose of tirzepatide is 5 mg regardless of prior GLP-1 receptor agonist exposure. 1

Rationale for Direct Switching

• The FDA-approved starting dose for tirzepatide is 5 mg weekly, designed to minimize gastrointestinal adverse events while providing therapeutic benefit, and this dose applies to all patients including those switching from other GLP-1 receptor agonists. 1

• Clinical trial evidence supports direct switching: in the SURPASS J-mono trial, patients were started on tirzepatide 2.5 mg for 4 weeks then escalated to 5 mg, but this initial 2.5 mg dose is not commercially available—the 5 mg starting dose is the standard approach. 2

• Real-world prospective data demonstrate that patients switching directly from GLP-1 receptor agonists (including dulaglutide 1.5 mg, 3.0 mg, and 4.5 mg) to tirzepatide 5 mg experienced improved glycemic control (HbA1c reduction of -0.43%) and additional weight loss (-2.15 kg) over 12 weeks with acceptable tolerability. 3

Switching Protocol

• Discontinue dulaglutide 4.5 mg and initiate tirzepatide 5 mg the following week (one week after the last dulaglutide dose), as dulaglutide has a terminal elimination half-life of 5 days and reaches steady state between the second and fourth doses. 4

• The 5 mg dose should be maintained for at least 4 weeks before considering escalation to 10 mg or 15 mg based on glycemic response and tolerability, following the standard tirzepatide titration schedule. 1

Expected Clinical Outcomes

• Patients switching from dulaglutide to tirzepatide can expect superior HbA1c reduction: in the SURPASS-SWITCH trial, switching to tirzepatide 15 mg (or maximum tolerated dose) produced an additional -0.77% HbA1c reduction compared to escalating dulaglutide to 4.5 mg. 5

• Weight loss will be substantially greater with tirzepatide: the SURPASS-SWITCH trial demonstrated -6.9 kg additional weight loss with tirzepatide versus dulaglutide escalation at 40 weeks. 5

• In the SURPASS J-mono trial comparing tirzepatide directly to dulaglutide 0.75 mg, tirzepatide 5 mg achieved -2.4% HbA1c reduction and -5.8 kg weight loss versus -1.3% HbA1c reduction and -0.5 kg weight loss with dulaglutide at 52 weeks. 2

Concomitant Medication Adjustments

• If the patient is taking sulfonylureas, discontinue them entirely or reduce the dose by 50% before starting tirzepatide to prevent hypoglycemia. 6

• If the patient is on basal insulin, reduce the dose by approximately 20% when initiating tirzepatide; for patients with HbA1c <8%, consider a more aggressive 30% reduction. 1

• Discontinue any DPP-4 inhibitors (sitagliptin, linagliptin) before starting tirzepatide, as concurrent use provides no additional benefit. 1

Safety Monitoring During Transition

• Assess the patient every 4 weeks during the first 12 weeks for gastrointestinal tolerance (nausea, diarrhea, vomiting), weight loss progress, blood pressure, and signs of pancreatitis or gallbladder disease. 1

• Gastrointestinal adverse events occur in approximately 13% of patients switching from GLP-1 receptor agonists to tirzepatide 5 mg, with nausea (12-20%), constipation (14-18%), and diarrhea (13-16%) being most common, but these are typically mild-to-moderate and transient. 2, 3

• Monitor for hypoglycemia if the patient is on insulin or sulfonylureas; tirzepatide alone carries minimal intrinsic hypoglycemia risk when used as monotherapy. 1

Contraindications and Precautions

• Screen for absolute contraindications before switching: personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN 2). 1

• Use caution in patients with a history of pancreatitis, severe gastroparesis, or recent heart failure decompensation, though these are relative rather than absolute contraindications. 1

Common Pitfalls to Avoid

• Do not restart dulaglutide titration or use a lower tirzepatide dose than 5 mg—the 5 mg starting dose is appropriate even for patients on high-dose dulaglutide. 1, 3

• Do not delay the switch due to concerns about tolerability—real-world data show that patients switching from dulaglutide 4.5 mg tolerate tirzepatide 5 mg well, with only 2% discontinuing due to adverse events in the first 12 weeks. 3

• Do not overlook the need to reduce or discontinue sulfonylureas and insulin, as the combination with tirzepatide significantly increases hypoglycemia risk. 1, 6