Lowest Dose of Tirzepatide
The lowest dose of tirzepatide is 2.5 mg subcutaneously once weekly, which serves exclusively as an initiation dose and is not approved for maintenance therapy. 1
Dosing Initiation Protocol
- All patients must start at 2.5 mg once weekly for 4 weeks, regardless of indication (obesity, weight management, or obstructive sleep apnea). 1
- This 2.5 mg starting dose is designed specifically for treatment initiation to minimize gastrointestinal adverse reactions and is explicitly not approved as a maintenance dosage. 1
- The initiation period allows for physiologic adaptation, as gastrointestinal side effects (nausea, vomiting, diarrhea) are most common during dose escalation and occur primarily in the first 20 weeks of treatment. 2, 3
Dose Escalation Requirements
After the mandatory 4-week initiation period at 2.5 mg:
- Increase to 5 mg once weekly, which represents the first approved maintenance dose. 1
- Further escalation may proceed in 2.5 mg increments (to 7.5 mg, 10 mg, 12.5 mg, or 15 mg) after at least 4 weeks at each dose level. 1
- The decision to escalate should be based on treatment response and tolerability, with the option to maintain a lower dose if gastrointestinal side effects are problematic. 1
Clinical Context for Low-Dose Initiation
The rationale for mandatory low-dose initiation is supported by dose-dependent adverse event data:
- Gastrointestinal adverse events increase with dose: 39% at 5 mg, 46% at 10 mg, and 49% at 15 mg. 2
- Drug discontinuation due to adverse events is highest at 15 mg (10%), compared to lower rates at 5 mg (4.3%) and 10 mg (7.1%). 2, 4
- Most gastrointestinal adverse events are mild to moderate in severity and occur during the dose-escalation period. 3, 4
Important Caveats
- Never use 2.5 mg as a long-term maintenance dose—this is a critical prescribing error as it is not approved for ongoing therapy. 1
- If a patient cannot tolerate escalation beyond 5 mg, maintaining at 5 mg is acceptable, as this dose still provides substantial weight reduction (mean -15.0% at 72 weeks). 4
- The 2.5 mg dose has no published efficacy data for weight loss or glycemic control, as clinical trials only evaluated maintenance doses of 5 mg, 10 mg, and 15 mg. 4, 5