Mounjaro (Tirzepatide) Starting Dose and Titration
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 efficacy and tolerability. 1, 2
Standard Titration Schedule
The FDA-approved titration follows a stepwise escalation over 16-20 weeks 1, 2:
- Weeks 1-4: 2.5 mg once weekly (starting dose to minimize GI side effects) 1, 2
- Weeks 5-8: 5 mg once weekly 1, 2
- Weeks 9-12: 7.5 mg once weekly (if escalating beyond 5 mg) 1, 2
- Weeks 13-16: 10 mg once weekly (if escalating beyond 7.5 mg) 1, 2
- Weeks 17-20: 15 mg once weekly (maximum dose) 1, 2
The 2.5 mg starting dose is not a maintenance dose—it exists solely to improve gastrointestinal tolerability during initiation 1, 2.
Maintenance Dosing
Your target maintenance dose depends on treatment goals 1:
- 5 mg weekly: Produces 15.0% weight loss at 72 weeks 1
- 10 mg weekly: Achieves intermediate efficacy 1
- 15 mg weekly: Maximum efficacy with 20.9% weight loss at 72 weeks 1
For type 2 diabetes, all three maintenance doses produce robust HbA1c reductions of 1.87-2.59%, with higher doses showing incrementally greater glucose-lowering effects 3, 4.
Monitoring During Titration
Assess patients at specific intervals to optimize outcomes 1, 2:
- Monthly (first 3 months): Evaluate gastrointestinal tolerance, weight loss progress, blood pressure, and signs of pancreatitis or gallbladder disease 1, 2
- Week 12-16: Formal efficacy assessment on maximum tolerated dose; discontinue if <4-5% weight loss 1
- Quarterly (after maintenance): Monitor weight stability, cardiovascular risk factors, and medication adherence 1
Concomitant Medication Adjustments
When initiating tirzepatide, proactively adjust diabetes medications to prevent hypoglycemia 1:
- Basal insulin: Reduce by 20% immediately (e.g., 12 units → 10 units daily); consider 30% reduction if HbA1c <8% 1
- Sulfonylureas: Discontinue entirely or reduce dose by 50% before starting tirzepatide 1
- DPP-4 inhibitors: Stop completely—no additional benefit when combined with tirzepatide 1
Common Pitfalls to Avoid
- Do not skip the 2.5 mg starting dose—initiating at 5 mg or higher markedly increases nausea (17-31%), vomiting (6-12%), and discontinuation rates 2, 4
- Do not escalate faster than every 4 weeks—premature dose increases before GI adaptation leads to intolerable side effects 1, 2
- Do not continue escalating if severe GI symptoms persist—maintain the current dose for an additional 4 weeks or consider permanent dose reduction 2
- Do not overlook insulin/sulfonylurea adjustments—failure to reduce these agents causes preventable hypoglycemia 1
Special Populations
- Renal impairment: No dose adjustment required across all CKD stages, but use caution during dose escalation due to dehydration risk from GI side effects 1, 2
- Oral contraceptives: Advise non-oral contraception or barrier method addition for 4 weeks after each dose escalation due to delayed gastric emptying affecting oral medication absorption 1, 2
- Narrow therapeutic index drugs (warfarin, digoxin): Monitor closely during titration as delayed gastric emptying may alter absorption 1, 2
Dose-Dependent Adverse Effects
Gastrointestinal symptoms are dose-dependent but typically resolve within 4-8 weeks 2, 4:
- Nausea: 17% (5 mg) → 22% (10 mg) → 31% (15 mg) 2, 4
- Diarrhea: 12% (5 mg) → 16% (10 mg) → 23% (15 mg) 2
- Vomiting: 6% (5 mg) → 10% (10 mg) → 12% (15 mg) 2, 4
Discontinuation rates increase with higher doses (relative risk 1.75 for 10 mg, 2.03 for 15 mg versus placebo), but overall serious adverse event rates do not differ significantly across doses 2.