First Week of Zepbound (Tirzepatide) Treatment
Patients starting Zepbound should expect to receive a 2.5 mg subcutaneous injection once weekly for the entire first 4 weeks, with the primary goal of allowing the body to adjust to the medication rather than achieving maximum therapeutic effect during this initial period. 1
Dosing During Week 1
- The starting dose is 2.5 mg administered subcutaneously once weekly for the first 4 weeks 1
- This injection can be given at any time of day, with or without meals, providing flexibility for patient convenience 1
- The 2.5 mg starting dose is specifically designed as a dose-escalation step to improve tolerability, not as a therapeutic dose 1
Expected Side Effects in the First Week
Gastrointestinal symptoms are the most common side effects patients will experience, though they tend to be mild to moderate in severity and occur primarily during this dose-escalation period 1, 2:
- Nausea: 10-31% of patients (dose-dependent) 1
- Diarrhea: 7-23% of patients 1
- Vomiting: 2-12% of patients 1
- Constipation: 3-5% of patients 1
- Abdominal pain: 3-5% of patients 1
- Decreased appetite: commonly reported 2
These gastrointestinal effects are consistent with the GLP-1 receptor agonist class and typically improve over time as the body adjusts to the medication 2, 3.
What Patients Should Monitor
Patients should be aware of potential acute kidney injury risk, particularly if experiencing severe gastrointestinal symptoms leading to dehydration 1:
- Maintain adequate hydration, especially if experiencing nausea, vomiting, or diarrhea 1
- Contact healthcare provider if unable to maintain fluid intake 1
Watch for signs of pancreatitis (though rare), including severe abdominal pain that may radiate to the back 1:
- Discontinue medication and seek immediate medical attention if pancreatitis is suspected 1
Realistic Expectations for Week 1
- Minimal weight loss or glycemic improvement should be expected during the first week, as the 2.5 mg dose is a starter dose 1
- The medication has an elimination half-life of 5 days, meaning it takes time to reach steady-state levels in the body 1
- Significant therapeutic effects typically emerge after dose escalation to 5 mg or higher, which occurs after completing the initial 4-week period at 2.5 mg 1
Special Considerations
No dose adjustments are required for patients with renal impairment, including those with severe kidney disease 4, 1. However, caution is still advised when initiating therapy in patients with kidney disease due to the potential dehydration risk from gastrointestinal side effects 1.
The medication affects gastric emptying, which patients should be aware of if they have any upcoming procedures or surgeries 1.