What is the recommended tirzepatide (Zepbound) dosing and titration schedule for adults with type 2 diabetes or obesity, and for children ≥ 10 years with type 2 diabetes, including safety precautions?

Tirzepatide Dosing and Titration

Tirzepatide should be initiated at 2.5 mg subcutaneously once weekly for 4 weeks, then increased to 5 mg weekly for at least 4 weeks, with further escalation to 10 mg and ultimately 15 mg weekly at 4-week intervals based on glycemic response and tolerability. 1

Standard Dosing Schedule

For Type 2 Diabetes (Mounjaro)

• Weeks 1-4: 2.5 mg subcutaneously once weekly (tolerability assessment dose, not therapeutic) 1
• Weeks 5-8: 5 mg once weekly (first therapeutic dose) 1
• Weeks 9-12: 10 mg once weekly (if additional glycemic control needed) 1
• Week 13+: 15 mg once weekly (maximum dose for optimal efficacy) 1

The 2.5 mg starting dose is specifically designed to minimize gastrointestinal adverse effects and is not intended for glycemic efficacy—treatment response should only be evaluated after reaching therapeutic doses of 5 mg or higher 1.

For Obesity (Zepbound)

• Weeks 1-4: 2.5 mg once weekly 1
• Weeks 5-8: 5 mg once weekly 1
• Weeks 9-12: 7.5 mg once weekly 1
• Weeks 13-16: 10 mg once weekly 1
• Weeks 17-20: 12.5 mg once weekly 1
• Week 21+: 15 mg once weekly (maintenance) 1

Administration Guidelines

• Injection site: Administer subcutaneously in the abdomen, thigh, or upper arm 2
• Timing: Once weekly on the same day each week, at any time of day, with or without meals 1
• Flexibility: The weekly injection day can be changed if at least 3 days (72 hours) have elapsed between doses 1

Missed Dose Management

• If ≤4 days since missed dose: Administer as soon as possible and resume regular weekly schedule 2
• If >4 days since missed dose: Skip the missed dose and give the next dose on the regularly scheduled day 2
• If 2 consecutive doses missed: Resume at the same dose if previously tolerated well 2
• If ≥3 consecutive doses missed: Consider restarting the titration schedule from 2.5 mg to minimize gastrointestinal side effects 2

Concomitant Medication Adjustments

Insulin Management

When initiating tirzepatide in patients on insulin 2:

• Reduce basal insulin by 20% immediately (e.g., from 12 units to 10 units daily) 2
• For HbA1c <8%: Consider a more aggressive 30% reduction (e.g., from 12 units to 8 units) 2
• Prandial insulin: Strongly consider discontinuing entirely, or reduce each dose by 50% (e.g., from 6 units to 3 units three times daily) and plan to discontinue within 2-4 weeks 2

Sulfonylurea Management

• Discontinue sulfonylureas entirely or reduce dose by 50% before starting tirzepatide to prevent hypoglycemia 2
• Reassess need for sulfonylurea after approximately 3 months, as tirzepatide frequently achieves adequate glycemic control alone 2

DPP-4 Inhibitors

• Stop all DPP-4 inhibitors (sitagliptin, linagliptin, etc.) before initiating tirzepatide—concurrent use provides no additional benefit 2

Monitoring Requirements

During Titration (Weeks 1-20)

• Every 4 weeks: Assess gastrointestinal tolerance, weight loss progress, blood pressure, fasting glucose, and signs of pancreatitis or gallbladder disease 2
• Glucose monitoring: Check fasting glucose daily and pre-meal glucose before each meal for the first 2 weeks if on insulin or sulfonylureas 2

After Reaching Maintenance Dose

• Every 3 months minimum: Monitor weight, HbA1c, blood pressure, cardiovascular risk factors, and medication adherence 1, 2
• Treatment response evaluation at 12-16 weeks: Discontinue if <5% weight loss after 3 months on maximum tolerated therapeutic dose 1

Renal Dosing

No dose adjustment is required for tirzepatide across all stages of chronic kidney disease, including eGFR <30 mL/min/1.73 m² and end-stage renal disease. 2 This makes tirzepatide a preferred option in advanced CKD, though vigilance for dehydration from gastrointestinal side effects is warranted 2.

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma 1, 2
• Multiple endocrine neoplasia syndrome type 2 (MEN 2) 1, 2
• History of severe hypersensitivity reaction to tirzepatide 2

Common Pitfalls to Avoid

• Do not assess weight loss efficacy at 1 month on the 2.5 mg starting dose—this dose is for tolerability only, not therapeutic effect 1
• Do not advance to the next dose if persistent severe abdominal pain or signs of pancreatitis develop—discontinue immediately 2
• Do not combine tirzepatide with other GLP-1 receptor agonists or DPP-4 inhibitors—no additional benefit and increased adverse effects 2
• Do not skip the gradual titration—starting at higher doses markedly increases gastrointestinal adverse events and discontinuation rates 2

Expected Outcomes

• Weight loss: Mean reduction of 20.9% at 72 weeks with the 15 mg dose in non-diabetic patients with obesity 1
• Glycemic control: HbA1c reductions of 1.87-2.59% across the SURPASS trials, with 23.0-62.4% of patients achieving HbA1c <5.7% (normal range) 1, 3, 4
• Cardiometabolic benefits: Reductions in blood pressure, waist circumference, triglycerides, and liver fat content 1, 3, 4