Zepbound Dosing: Starting with Half the Lowest Dose
No, patients should not start with half of the lowest dose of Zepbound (tirzepatide). The FDA-approved dosing regimen for Zepbound requires initiation at 2.5 mg subcutaneously once weekly, which is already designed as a starter dose to improve tolerability before escalation.
Standard Dosing Protocol
The lowest approved dose of Zepbound is 2.5 mg once weekly, which serves as the mandatory starting dose for all patients to minimize gastrointestinal side effects during treatment initiation (based on FDA labeling standards for GLP-1 receptor agonists).
After 4 weeks at 2.5 mg, the dose should be increased to 5 mg once weekly, with subsequent escalations in 2.5 mg increments every 4 weeks as tolerated, up to a maximum of 15 mg once weekly (standard GLP-1 agonist titration protocol).
Renal Impairment Considerations
No dose adjustment is required for Zepbound in patients with any degree of renal impairment, including end-stage renal disease, as GLP-1 receptor agonists are primarily eliminated through protein catabolism rather than renal excretion (similar to other peptide-based medications).
The evidence shows that severe renal impairment does not result in clinically significant drug accumulation for peptide-based therapeutics like GLP-1 agonists 1.
Unlike renally-cleared medications that require dose reduction (such as clarithromycin requiring 50% reduction when creatinine clearance <60 mL/min 2), peptide hormones maintain standard dosing across all levels of renal function.
Why Half-Dosing Is Not Appropriate
Splitting the starter dose below 2.5 mg would result in subtherapeutic drug exposure that has not been studied for safety or efficacy in clinical trials.
The 2.5 mg starting dose already represents a carefully calibrated balance between minimizing side effects and achieving therapeutic benefit.
There is no pharmacokinetic rationale for dose reduction below the approved starting dose, even in special populations 3.
Common Pitfalls to Avoid
Do not extrapolate dosing strategies from renally-cleared medications (like aminoglycosides or ethambutol that require dose adjustment 4) to peptide-based drugs with hepatic/proteolytic elimination.
Avoid the temptation to "start low and go slow" below FDA-approved starting doses without evidence-based justification, as this may delay therapeutic benefit without improving tolerability.
If gastrointestinal side effects are a concern, maintain the 2.5 mg dose for a longer duration (6-8 weeks instead of 4 weeks) before escalation, rather than reducing below the approved starting dose.