Tirzepatide (Mounjaro) Dosing Recommendations
The recommended dosing for Mounjaro (tirzepatide) starts at 2.5 mg subcutaneously once weekly for 4 weeks, then increases gradually to a maintenance dose of 5 mg, 10 mg, or 15 mg once weekly depending on glycemic control and tolerability.
Initial Dosing and Titration Schedule
Tirzepatide follows a specific dose escalation protocol to minimize gastrointestinal side effects:
- Starting dose: 2.5 mg subcutaneously once weekly for 4 weeks
- First increase: 5 mg once weekly for at least 4 weeks
- Second increase: 10 mg once weekly for at least 4 weeks (if needed)
- Maximum dose: 15 mg once weekly (if needed)
Dose Selection Considerations
The optimal maintenance dose should be determined based on:
- Glycemic response
- Weight loss goals
- Tolerability of side effects
- Comorbid conditions
Administration Guidelines
- Administer subcutaneously in the abdomen, thigh, or upper arm
- Can be administered at any time of day, with or without meals
- Maintain consistent day of the week for administration
- If a dose is missed, administer within 4 days of the scheduled dose; if more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day
Renal Impairment Considerations
- No dose adjustment is necessary for mild to moderate renal impairment
- Limited data available for severe renal impairment or end-stage renal disease
Common Side Effects and Management
Gastrointestinal side effects are most common, particularly during dose escalation:
- Nausea (37-43%)
- Diarrhea (22-24%)
- Vomiting (15-24%)
- Constipation (12-17%)
These effects typically decrease over time and can be managed by:
- Following the recommended dose escalation schedule
- Taking anti-emetics if needed
- Maintaining adequate hydration
- Consuming smaller, more frequent meals
Special Considerations
- Perioperative management: Due to effects on gastric emptying, consider holding tirzepatide before elective procedures to minimize risk of pulmonary aspiration 1
- Medication interactions: Monitor for potential consequences of delayed absorption of oral medications with narrow therapeutic index
Clinical Pearls
- The 15 mg dose provides the greatest weight loss and glycemic control benefits
- Most gastrointestinal side effects occur during the dose escalation period
- Tirzepatide has demonstrated superior weight loss compared to semaglutide in clinical trials 2
- Consider the long half-life (approximately 5 days) when planning treatment interruptions or discontinuation
Monitoring Recommendations
- Evaluate glycemic response and weight loss at each dose level
- Assess tolerability before each dose increase
- Consider delaying dose increases if significant gastrointestinal side effects occur
Tirzepatide represents a significant advancement in the treatment of type 2 diabetes and obesity, with clinical trials demonstrating substantial reductions in HbA1c and body weight at the recommended doses.