How to Dose Tirzepatide
Start tirzepatide at 2.5 mg subcutaneously once weekly, then escalate by 2.5 mg every 4 weeks until reaching a maintenance dose of 5 mg, 10 mg, or 15 mg based on tolerability, with the 15 mg dose providing maximum efficacy for both glycemic control and weight loss. 1, 2
Initial Dosing and Titration Schedule
- Begin with 2.5 mg subcutaneously once weekly for the first 4 weeks to minimize gastrointestinal side effects 2, 3
- Increase by 2.5 mg increments every 4 weeks until the assigned maintenance dose is achieved 2, 3
- FDA-approved maintenance doses are 5 mg, 10 mg, or 15 mg once weekly 1, 2
- The gradual dose escalation strategy is critical—rushing this process significantly increases gastrointestinal adverse events 1
Target Dose Selection
Target the 15 mg dose if tolerated, as it provides superior outcomes across all metrics. 2
- The 15 mg dose achieves 20.9% weight loss at 72 weeks, compared to 19.5% with 10 mg and 15.0% with 5 mg 1, 4
- Higher doses (10 mg and 15 mg) provide superior glycemic control with greater HbA1c reductions than lower doses 5, 2
- The 15 mg dose demonstrated 5.1% greater weight loss than semaglutide 2.4 mg, establishing it as the most effective single agent for weight reduction 5, 2
Monitoring During Dose Escalation
- Assess effectiveness and safety at least monthly for the first 3 months during dose escalation 1, 2
- Evaluate treatment efficacy at 12-16 weeks on the maximum tolerated dose 2
- Consider discontinuation if less than 4-5% body weight loss at 16 weeks on maximum tolerated dose 2
- Monitor quarterly thereafter once maintenance dose is established 1
Common Adverse Events by Dose
Gastrointestinal side effects are dose-dependent and most common during escalation 1, 3:
- Nausea: 13-18% overall, ranging from 17-31% depending on dose 1, 2, 3
- Constipation: 12-18% of patients 1, 2
- Diarrhea: 12-17% of patients 1, 2
- Decreased appetite: 10-12% of patients 1, 2
- Vomiting: 12% of patients, with dose-dependent frequency 2
These adverse events are typically mild to moderate in severity and decrease over time 3, 6
Special Population Considerations
Renal Impairment
- No dose adjustment necessary for mild to moderate renal impairment 1
- Use caution when initiating or escalating doses in patients with renal impairment due to potential risk of acute kidney injury 5
Perioperative Management
Oral Contraception
- Advise patients using oral hormonal contraceptives to switch to or add a non-oral contraception method for 4 weeks after initiation and after each dose escalation 1, 5, 2
Drug Interactions
- Monitor medications with narrow therapeutic indices (e.g., warfarin) closely during treatment, as tirzepatide delays gastric emptying and may affect absorption 5, 2
Critical Safety Contraindications
- Do not use in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 2
- Discontinue immediately if pancreatitis is suspected 2
- Risk of thyroid C-cell tumors demonstrated in rodents, though human relevance remains undetermined 2