Mounjaro (Tirzepatide) Dosing
Mounjaro is administered as a once-weekly subcutaneous injection starting at 2.5 mg, with dose escalation by 2.5 mg every 4 weeks until reaching the target maintenance dose of 5 mg, 10 mg, or 15 mg weekly, depending on glycemic control needs and tolerability. 1
Starting and Titration Schedule
- Initial dose: 2.5 mg subcutaneously once weekly 2
- Dose escalation: Increase by 2.5 mg every 4 weeks 2
- Maintenance doses: 5 mg, 10 mg, or 15 mg once weekly 1, 2
The gradual titration schedule is critical to minimize gastrointestinal side effects, which are most common during the dose-escalation period in the first 20 weeks of treatment 3.
Maintenance Dosing by Indication
For Type 2 Diabetes
- Dose range: 5 mg to 15 mg once weekly 1
- The maximum approved dose is 15 mg weekly 1
- Higher doses provide superior glycemic control and weight reduction 2, 4
In the SURPASS trials, mean HbA1c reductions ranged from 1.24% to 2.58%, with 23.0% to 62.4% of patients achieving HbA1c <5.7% (normoglycemia) 5. Weight loss ranged from 5.4 to 11.7 kg across the dose range 5.
For Weight Management
- Dose range: 5 mg, 10 mg, or 15 mg once weekly 1
- At 176 weeks, mean weight reduction was -12.3% with 5 mg, -18.7% with 10 mg, and -19.7% with 15 mg 3
Administration Details
- Route: Subcutaneous injection 1
- Frequency: Once weekly 1
- Formulation: Available as single-dose prefilled pens and single-dose vials 4
- Timing: Can be administered at any time of day, with or without meals 4
Pharmacokinetic Considerations
- Half-life: 5 days 1
- Bioavailability: 80% 1
- Volume of distribution: 10.3 liters 1
- Elimination: Metabolized; no dose adjustment necessary for renal impairment 1
The long half-life of 5 days supports once-weekly dosing and means steady-state concentrations are achieved after approximately 4 weeks 1.
Dose-Dependent Efficacy
Higher doses provide incrementally greater benefits 2, 5:
- 5 mg: HbA1c reduction of 1.87%, weight loss of 3.8 kg (5.1%) 2
- 10 mg: HbA1c reduction of 2.59%, weight loss of 7.5 kg (10.1%) 2
- 15 mg: HbA1c reduction of 2.93%, weight loss of 10.2 kg (13.2%) 2
Tirzepatide demonstrated superior efficacy compared to semaglutide 1 mg weekly and basal insulin in head-to-head trials 4, 5.
Common Pitfalls and Caveats
Do not skip the titration schedule: Rapid dose escalation significantly increases gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation), which are the most common reasons for treatment discontinuation 2, 4, 3.
Peri-operative management: Due to delayed gastric emptying effects, consider holding tirzepatide for one week before elective procedures requiring anesthesia to minimize aspiration risk 1. The elimination half-life of 5 days means drug effects persist well beyond the last injection 1.
Gastrointestinal tolerability: Most adverse events are mild to moderate and occur primarily during dose escalation in the first 20 weeks 3. Treatment-emergent adverse events were more frequent with the 15 mg dose (84%) compared to 5 mg (74%) and 10 mg (74%) 2.
No renal dose adjustment required: Unlike many diabetes medications, tirzepatide does not require dose modification in renal impairment 1.