Tirzepatide Starting and Titration Dose
Start tirzepatide at 2.5 mg subcutaneously once weekly, then escalate by 2.5 mg every 4 weeks until reaching the target maintenance dose of 5 mg, 10 mg, or 15 mg based on efficacy and tolerability. 1, 2, 3
Standard Dosing Protocol
Initial Dosing
- All patients begin at 2.5 mg subcutaneously once weekly regardless of their target maintenance dose 2, 3
- This starting dose is used for the first 4 weeks to minimize gastrointestinal side effects 1
Dose Escalation Schedule
- Increase by 2.5 mg increments every 4 weeks until the assigned maintenance dose is reached 2, 3
- For patients targeting 5 mg: escalate from 2.5 mg to 5 mg at week 4 3
- For patients targeting 10 mg: escalate 2.5 mg → 5 mg → 7.5 mg → 10 mg (reaching target at week 12) 2, 3
- For patients targeting 15 mg: escalate 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg (reaching target at week 20) 2, 3
Maintenance Dosing
- FDA-approved maintenance doses are 5 mg, 10 mg, or 15 mg once weekly 1
- The 15 mg dose provides maximum efficacy with 20.9% weight loss at 72 weeks compared to 15.0% with 5 mg 1
- Higher doses produce significantly greater HbA1c reductions: -2.4% with 5 mg, -2.6% with 10 mg, and -2.8% with 15 mg at 52 weeks 3
Dose-Dependent Effects
The evidence clearly demonstrates a dose-response relationship for both glycemic control and weight loss 3, 4. In the SURPASS J-mono trial, tirzepatide showed superior efficacy at higher doses, with the 15 mg dose reducing HbA1c by 1.5 percentage points more than dulaglutide 0.75 mg 3. Weight loss is similarly dose-dependent, ranging from 5.4 kg at 5 mg to 11.7 kg at 15 mg 4.
Monitoring During Titration
- Assess effectiveness and safety at least monthly for the first 3 months during dose escalation 1
- After reaching maintenance dose, monitor at least quarterly 1
- Evaluate treatment efficacy at 12-16 weeks on the maximum tolerated dose 5
- Consider discontinuation if less than 4-5% body weight loss at 16 weeks on maximum tolerated dose 5
Common Adverse Events During Titration
Gastrointestinal Effects
- Nausea occurs in 12-20% of patients and is dose-dependent 3
- Constipation affects 12-18% of patients 1
- Diarrhea occurs in 12-17% of patients 1
- Decreased appetite affects 10-12% of patients 1, 2
These adverse events are typically mild to moderate and most frequent during dose escalation 2, 3. The gradual 4-week titration schedule is specifically designed to minimize these gastrointestinal side effects 1.
Special 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 acute kidney injury risk 6
Contraception
- Advise non-oral contraception or addition of non-oral method for 4 weeks after each dose escalation for patients using oral hormonal contraceptives, as tirzepatide may delay gastric emptying and affect oral medication absorption 1, 6
Drug Interactions
- Monitor medications with narrow therapeutic indices (e.g., warfarin) closely during titration due to potential delayed absorption from gastric emptying effects 6