What is the recommended titration schedule for Mounjaro (tirzepatide) and how should the dose be increased?

Mounjaro (Tirzepatide) Dosing and Titration Schedule

Start tirzepatide at 2.5 mg subcutaneously once weekly for the first 4 weeks, then increase by 2.5 mg every 4 weeks until reaching your target maintenance dose of 5 mg, 10 mg, or 15 mg based on your response and tolerability. 1, 2

Standard Titration Protocol

The FDA-approved escalation schedule follows a strict 4-week interval between dose increases to minimize gastrointestinal side effects while building therapeutic efficacy 1, 2:

• Weeks 1–4: 2.5 mg once weekly (this is a tolerability dose, not therapeutic) 1, 3
• Weeks 5–8: 5 mg once weekly (first maintenance dose) 1, 2
• Weeks 9–12: 10 mg once weekly (if additional efficacy needed) 1, 2
• Weeks 13+: 15 mg once weekly (maximum approved dose for greatest weight loss) 1, 2

The 2.5 mg starting dose exists solely to assess gastrointestinal tolerance—do not expect meaningful weight loss or glycemic improvement at this dose 3. The 5 mg dose is your first therapeutic maintenance dose 1, 2.

When to Increase the Dose

Increase to the next dose level after a minimum of 4 weeks if:

• You have tolerated the current dose without significant nausea, vomiting, or diarrhea 2
• Your HbA1c remains above your individualized target (typically <7% for most adults with diabetes) after 12 weeks on a given dose 1
• You need additional weight loss and have not achieved at least 5% total body weight reduction after 3–4 months on the current dose 1, 3
• Weight loss has plateaued completely for 8–12 weeks despite continued adherence to diet and exercise 3

Do not increase the dose if:

• You are experiencing persistent moderate-to-severe gastrointestinal symptoms 2
• You have already achieved your glycemic target (HbA1c <7%) and are satisfied with your weight loss 1
• You are on the 15 mg dose—this is the maximum approved weekly dose 1, 2

Monitoring During Titration

Assess patients every 4 weeks during dose escalation to evaluate 2:

• Gastrointestinal tolerance (nausea, vomiting, diarrhea, constipation)
• Weight loss progress
• Blood pressure (may decrease as weight drops, requiring antihypertensive adjustment) 1
• Signs of pancreatitis (persistent severe abdominal pain) 1, 2
• Signs of gallbladder disease (right-upper-quadrant pain, fever) 1, 2

After reaching your maintenance dose, monitor at least every 3 months for weight stability, HbA1c (if diabetic), cardiovascular risk factors, and medication adherence 1.

Expected Efficacy by Dose

The weight loss and glycemic benefits are dose-dependent 1, 3:

• 5 mg weekly: Mean weight loss ~12–15% at 72 weeks in non-diabetic patients 3
• 10 mg weekly: Mean weight loss ~15–18% at 72 weeks 3
• 15 mg weekly: Mean weight loss ~20.9% at 72 weeks (the most potent dose) 1, 3

For diabetes, increasing from 5 mg to 10 mg typically lowers HbA1c by an additional 0.3–0.5 percentage points 1. The 15 mg dose produces HbA1c reductions of 2.3–2.6% from baseline 4, 5.

Common Pitfalls to Avoid

• Do not skip the 4-week interval between dose increases—rushing titration dramatically increases nausea, vomiting, and treatment discontinuation 2
• Do not stay on 2.5 mg expecting weight loss—this is only a starter dose for tolerability 3
• Do not increase the dose if you are already losing weight steadily and tolerating the current dose well—the lowest effective dose minimizes side effects and cost 3
• Do not declare treatment failure before reaching 12–16 weeks on a therapeutic dose (5 mg or higher)—early assessment leads to premature discontinuation 1, 3

Concomitant Medication Adjustments

When starting tirzepatide, immediately adjust these medications to prevent hypoglycemia 1:

• Basal insulin: Reduce by 20% (e.g., 12 units → 10 units daily) 1
• Sulfonylureas: Reduce by 50% or discontinue entirely 1
• DPP-4 inhibitors: Stop completely—no additional benefit when combined with tirzepatide 1

Special Populations

• Chronic kidney disease: No dose adjustment required at any eGFR level, including eGFR <30 mL/min/1.73 m² 1
• Oral contraceptives: Add a non-oral contraceptive method for 4 weeks after each dose increase due to delayed gastric emptying affecting absorption 2
• Narrow therapeutic index drugs (e.g., warfarin): Monitor closely during titration as delayed gastric emptying may alter absorption 2

Absolute Contraindications

Do not initiate tirzepatide if the patient has 1, 2:

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

When to Stop Dose Escalation

Discontinue tirzepatide or do not increase the dose further if 1, 2:

• Persistent severe abdominal pain develops (suspect pancreatitis)
• Right-upper-quadrant pain with fever occurs (suspect cholecystitis)
• Weight loss is <5% after 3 months on the maximum tolerated dose
• Severe gastrointestinal symptoms persist despite 4–8 weeks on the current dose