Mounjaro (Tirzepatide) Dosing
Start tirzepatide at 2.5 mg subcutaneously once weekly for 4 weeks, then increase to 5 mg once weekly, with further escalations to 10 mg and a maximum of 15 mg based on clinical response, each after at least 4 weeks at the prior dose. 1
Initial Dosing and Titration Schedule
- Begin with 2.5 mg subcutaneously once weekly for the first 4 weeks as the starting dose 1
- After 4 weeks, increase to 5 mg once weekly 1
- Further dose escalation to 10 mg once weekly can occur after at least 4 weeks on the 5 mg dose, based on clinical response and tolerability 1
- Maximum dose is 15 mg once weekly, which can be reached after at least 4 weeks on the 10 mg dose 1
Administration Guidelines
- Administer as a subcutaneous injection once weekly at any time of day, with or without meals 1
- The timing relative to meals does not affect efficacy, providing flexibility for patient convenience 1
- No dose adjustments are required for patients with renal impairment 1
Expected Clinical Outcomes
Weight Loss
- At 72 weeks, tirzepatide produces mean weight reductions of -12.8% with 10 mg and -14.7% with 15 mg in patients with type 2 diabetes and obesity 2
- In patients with obesity without diabetes, weight reductions reach -15.0% with 5 mg, -19.5% with 10 mg, and -20.9% with 15 mg 3
- 79-91% of patients achieve ≥5% weight loss, and 50-57% achieve ≥20% weight loss with the 10-15 mg doses 2, 3
Glycemic Control
- Tirzepatide reduces HbA1c by -1.87% to -2.59% (-20 to -28 mmol/mol) across clinical trials 4
Common Side Effects and Management
Gastrointestinal side effects are the most common adverse events and are typically mild to moderate:
- Nausea occurs in 10-31% of patients (dose-dependent) 1
- Diarrhea affects 7-23% of patients 1
- Vomiting occurs in 2-12% 1
- Constipation affects 3-5% and abdominal pain occurs in 3-5% 1
- These gastrointestinal effects occur primarily during the dose-escalation period in the first 20 weeks and typically resolve with continued use 3, 5
- Treatment discontinuation due to adverse events occurs in 4.3-7.1% of patients, with gastrointestinal issues being the primary cause 3
Critical Safety Warnings and Monitoring
Black Box Warning
- Tirzepatide carries a black box warning for thyroid C-cell tumors observed in rodent studies (human relevance not established) 1
- Contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 1
Pancreatitis Risk
- Monitor for signs and symptoms of pancreatitis (severe persistent abdominal pain radiating to the back, with or without vomiting) 1
- Discontinue tirzepatide immediately if pancreatitis is suspected 1
- Case reports document acute pancreatitis with temporal correlation to tirzepatide initiation, particularly in patients with pre-existing risk factors like gallstones 6
Acute Kidney Injury
- Use caution when initiating or escalating doses in patients with kidney disease due to potential risk of acute kidney injury, likely related to volume depletion from gastrointestinal side effects 1
- Ensure adequate hydration, especially during dose escalation 1
Special Considerations
Perioperative Management
- Consider the 5-day elimination half-life and effects on gastric emptying when planning surgical procedures 1
- Delayed gastric emptying may increase aspiration risk during anesthesia 1