Tirzepatide Dosing for Weight Loss
For weight loss in adults with obesity (BMI ≥30) or overweight (BMI ≥27 with weight-related comorbidities), tirzepatide should be started at 2.5 mg subcutaneously once weekly and titrated upward every 4 weeks to a maintenance dose of 5 mg, 10 mg, or 15 mg weekly, with the 15 mg dose producing the greatest weight loss of approximately 20.9% at 72 weeks. 1, 2, 3
Dosing Algorithm and Titration Schedule
The standard titration protocol follows this schedule: 2, 4
- Weeks 1-4: 2.5 mg once weekly (tolerability assessment dose, not therapeutic)
- Weeks 5-8: 5 mg once weekly (first therapeutic dose)
- Weeks 9-12: 7.5 mg once weekly
- Weeks 13-16: 10 mg once weekly
- Weeks 17-20: 12.5 mg once weekly
- Week 21 onward: 15 mg once weekly (maximum dose)
The slow titration minimizes gastrointestinal side effects, which are the most common adverse events (nausea 17-44%, diarrhea 12-32%, vomiting 7-25%). 1, 2, 5
Dose-Dependent Efficacy
Weight loss increases with higher doses: 2, 3, 6
- 5 mg weekly: 15.0% mean weight loss at 72 weeks
- 10 mg weekly: 19.5% mean weight loss at 72 weeks
- 15 mg weekly: 20.9% mean weight loss at 72 weeks (maximum efficacy)
- Placebo: 3.1% weight loss
Between 85-91% of patients achieve ≥5% weight loss, and 50-57% achieve ≥20% weight loss on the 10-15 mg doses, compared to only 3% with placebo. 1, 3
Duration of Treatment: Lifelong Use Required
Tirzepatide must be used indefinitely to maintain weight loss benefits—discontinuation results in rapid weight regain of approximately 50-67% of lost weight within one year. 1, 4 This is not a short-term intervention but a chronic disease management strategy, similar to medications for hypertension or diabetes. 1
Weight maintenance trials consistently demonstrate that stopping anti-obesity medications leads to rapid weight regain, making continuous long-term treatment essential for sustained benefits. 4 Patients should be counseled upfront that this is a lifelong commitment, not a temporary weight loss solution. 1
When to Assess Treatment Response
Evaluate efficacy at 12-16 weeks on the maximum tolerated therapeutic dose (not at one month on the starting dose). 2, 4 The 2.5 mg starting dose is solely for gastrointestinal tolerability assessment and should not be used to judge weight loss effectiveness. 4
Discontinue tirzepatide if: 4
- Less than 4-5% body weight loss after 16 weeks on a therapeutic dose (5 mg or higher)
- Weight loss plateaus completely for 8-12 weeks despite continued lifestyle modifications
- Intolerable adverse effects persist despite dose adjustment
Continue treatment if: 4
- ≥5% weight loss achieved after 3 months (early responders have better long-term outcomes)
- Continued weight loss trajectory is observed
- Good adherence to lifestyle modifications with no significant adverse effects
Monitoring Requirements
During titration (first 3-4 months): 2, 4
- Assess monthly for gastrointestinal tolerance, weight loss progress, and blood pressure
- Monitor for signs of pancreatitis (persistent severe abdominal pain)
- Monitor for gallbladder disease symptoms (right upper quadrant pain)
After reaching maintenance dose: 2, 4
- Assess at least quarterly for weight, blood pressure, cardiovascular risk factors
- Track weight monthly to ensure continued efficacy
- Monitor for delayed absorption of oral medications with narrow therapeutic indices
Absolute Contraindications
Do not prescribe tirzepatide if: 1, 2, 4
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2
- Severe gastroparesis or gastrointestinal motility disorders
Special Considerations
Renal impairment: 2
- eGFR >30 mL/min/1.73 m²: No dose adjustment required
- eGFR 15-30 mL/min/1.73 m²: Use caution when initiating or escalating doses due to acute kidney injury risk
- eGFR <15 mL/min/1.73 m² or dialysis: Avoid use (limited clinical experience)
Perioperative management: 1
- Discontinue at least 3 weeks before elective surgery requiring anesthesia due to delayed gastric emptying and aspiration risk
- Retained gastric contents documented even after extended fasting periods
Combination with lifestyle modifications is mandatory: 1, 2
- 500-kcal reduction below daily requirements
- Minimum 150 minutes/week of physical activity
- Resistance training to preserve lean body mass
Cost Considerations
The average wholesale price is approximately $1,272-$1,283 per 30-day supply, which may limit access depending on insurance coverage. 1, 2, 4 Insurance authorization can be challenging, particularly for obesity management without diabetes. 1
Comparison to Other Options
Tirzepatide produces superior weight loss compared to semaglutide 2.4 mg weekly (14.9% weight loss) and liraglutide 3.0 mg daily (5.2-6.1% weight loss), making it the most potent pharmacological option currently available for weight management. 1, 7, 3 The weight loss achieved with tirzepatide 15 mg is comparable to bariatric surgery outcomes. 4, 7