Tirzepatide Titration for a 280 lb Male
Start tirzepatide at 2.5 mg subcutaneously once weekly for 4 weeks, then escalate to 5 mg weekly for 4 weeks, followed by 10 mg weekly for 4 weeks, and finally reach the maximum dose of 15 mg weekly after 12 weeks of titration. 1, 2
Standard Titration Schedule
The FDA-approved titration protocol follows a gradual dose escalation every 4 weeks to minimize gastrointestinal adverse effects while achieving therapeutic benefit 1, 3:
- Weeks 1-4: 2.5 mg once weekly (tolerability dose, not therapeutic) 3
- Weeks 5-8: 5 mg once weekly (first therapeutic dose) 1, 2
- Weeks 9-12: 10 mg once weekly 1, 2
- Week 13 onward: 15 mg once weekly (maximum dose for optimal weight loss) 1, 2
Administration Details
Inject tirzepatide subcutaneously once weekly on the same day each week, at any time of day, with or without meals 3. The injection can be given at any consistent time that works for the patient's schedule 3.
Expected Outcomes
With this titration schedule, expect the following results:
- Weight loss: 20.9% total body weight reduction at 72 weeks with the 15 mg dose, translating to approximately 58 pounds for a 280 lb male 1, 2, 4
- Glycemic control (if diabetic): HbA1c reductions of 1.87-2.59%, with 23.0-62.4% of patients achieving HbA1c <5.7% 1, 5
- Cardiometabolic benefits: Reductions in blood pressure, triglycerides, and visceral adiposity 1, 5
Monitoring During Titration
Assess the patient every 4 weeks during dose escalation for 1, 3:
- Gastrointestinal tolerance (nausea, vomiting, diarrhea, constipation)
- Weight loss progress
- Blood pressure changes
- Signs of pancreatitis (persistent severe abdominal pain)
- Signs of gallbladder disease
Concomitant Medication Adjustments
If the patient is on other glucose-lowering medications 1, 2:
- Insulin: Reduce basal insulin by 20% when starting tirzepatide to prevent hypoglycemia 1
- Sulfonylureas: Discontinue or reduce dose by 50% due to increased hypoglycemia risk 1, 2
- DPP-4 inhibitors: Discontinue before starting tirzepatide (no additional benefit) 2
Treatment Evaluation Timepoint
Evaluate treatment efficacy at 12-16 weeks on the maximum tolerated therapeutic dose (5 mg, 10 mg, or 15 mg) 1, 3. Expect at least 5% body weight loss by 16 weeks to justify continuation 3. If weight loss is <5% after 3 months at therapeutic dose, consider discontinuation and alternative approaches 1, 3.
Common Pitfalls to Avoid
- Do not assess efficacy at 1 month: The 2.5 mg starting dose is for tolerability only, not weight loss efficacy 3
- Do not skip the titration schedule: Rapid dose escalation increases gastrointestinal adverse effects and discontinuation rates 1, 3
- Do not stop at 5 mg or 10 mg without clinical reason: Higher doses (15 mg) achieve superior weight loss (20.9% vs. lower percentages with smaller doses) 1, 2, 4
- Do not combine with other GLP-1 receptor agonists: This is pharmacologically redundant and potentially harmful 1
Absolute Contraindications
Do not prescribe tirzepatide if the patient has 1, 2:
- Personal or family history of medullary thyroid cancer
- Multiple endocrine neoplasia syndrome type 2 (MEN2)
Long-Term Considerations
Tirzepatide requires lifelong continuous use to maintain weight loss benefits 1, 3. Discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 1, 3. After reaching the maintenance dose of 15 mg weekly, monitor quarterly for weight stability, cardiovascular risk factors, and medication tolerance 1.