Tirzepatide Dosing for Weight Loss
For weight loss in adults with obesity (BMI ≥30) or overweight (BMI ≥27 with comorbidities), tirzepatide should be started at 5 mg weekly subcutaneously and titrated upward every 4 weeks to a maximum dose of 15 mg weekly, which can be continued indefinitely as lifelong treatment is necessary to maintain weight loss. 1, 2
Standard Dosing Protocol
Tirzepatide follows a structured dose escalation schedule over 12-16 weeks: 2
- Week 0-4: Start at 5 mg subcutaneously once weekly 2
- Week 5-8: Increase to 10 mg weekly if tolerated 2
- Week 9+: Increase to 15 mg weekly (maximum dose) if tolerated 2
The 15 mg dose provides maximum efficacy with 20.9% weight loss at 72 weeks, compared to 19.5% with 10 mg and 15.0% with 5 mg. 1, 2 This represents a 6% absolute advantage over semaglutide 2.4 mg weekly (14.9% weight loss). 1
Duration of Treatment
Tirzepatide must be used lifelong for sustained weight loss. 1 Sudden discontinuation results in regain of one-half to two-thirds of the weight loss within 1 year, making indefinite treatment necessary for maintained benefits. 1 After 3 years of continuous treatment, tirzepatide maintains substantial weight reduction with a markedly lower risk of progression to type 2 diabetes. 3
Early responders who achieve ≥5% weight loss after 3 months should continue long-term therapy unless clinical circumstances suggest otherwise. 1 If weight loss is <5% after 3 months at therapeutic dose, consider discontinuation and alternative approaches. 1
Administration Details
Tirzepatide is administered as a once-weekly subcutaneous injection, which can be given at any time of day, with or without meals, on the same day each week for optimal adherence. 1, 2 The gradual dose escalation every 4 weeks is designed to minimize gastrointestinal adverse events while providing therapeutic benefit. 2
Monitoring Requirements
Assess patients at least monthly for the first 3 months, then quarterly thereafter: 2
- Weight loss progress and cardiovascular risk factors 1
- Gastrointestinal tolerance (nausea occurs in 13-18% of patients) 2
- Blood pressure (may require antihypertensive adjustment) 1
- Signs of pancreatitis or gallbladder disease 1
Treatment efficacy should be evaluated at 12-16 weeks on the maximum tolerated therapeutic dose. 1
Absolute Contraindications
Do not prescribe tirzepatide in patients with: 1, 2
- Personal or family history of medullary thyroid cancer 1
- Multiple endocrine neoplasia syndrome type 2 1
Special Populations
No dose adjustment is required for renal impairment across all CKD stages, including eGFR <30 mL/min/1.73 m². 2 Tirzepatide can be used safely in patients with advanced kidney disease. 1
For women using oral contraceptives, advise switching to non-oral methods or adding barrier contraception for 4 weeks after initiation and each dose escalation, as tirzepatide may delay gastric emptying and affect absorption. 2
Common Pitfalls to Avoid
Do not combine tirzepatide with other GLP-1 receptor agonists or DPP-4 inhibitors due to overlapping mechanisms and lack of additional benefit. 1 If patients are on sulfonylureas or insulin, reduce those doses to prevent hypoglycemia. 1
Do not stop tirzepatide abruptly without counseling patients about inevitable weight regain. 1 If discontinuation is necessary, taper gradually, intensify lifestyle interventions immediately, and establish monthly weight monitoring for the first 6 months. 1
For elective surgery requiring anesthesia, discontinue tirzepatide at least 3 weeks before the procedure due to delayed gastric emptying and aspiration risk, even with extended fasting periods. 1
Cost Considerations
The medication costs approximately $1,272 per 30-day supply, requiring long-term financial planning as lifelong treatment is typically necessary. 1 Patients should be informed upfront about the indefinite duration and cost implications of treatment. 1