GFR Cut-off for Zepbound (Tirzepatide)
No dose adjustment of Zepbound is required for any level of renal impairment, including end-stage renal disease (ESRD). 1
Dosing Across All Levels of Renal Function
The FDA label explicitly states that no dosage adjustment of Zepbound is recommended for patients with renal impairment, as pharmacokinetic studies demonstrated no change in tirzepatide levels across all degrees of kidney dysfunction, including ESRD. 1
Standard dosing (starting at 2.5 mg subcutaneously once weekly, escalating to maintenance doses of 5-15 mg weekly) applies regardless of eGFR level. 1
Critical Monitoring Requirement
Monitor renal function closely in patients experiencing adverse reactions that could lead to volume depletion (such as nausea, vomiting, or diarrhea), as these gastrointestinal effects are common with GLP-1 receptor agonists and can precipitate acute kidney injury. 1
This monitoring is particularly important because tirzepatide's mechanism involves delayed gastric emptying and appetite suppression, which can reduce fluid intake while gastrointestinal side effects increase fluid losses. 1
Context Within Diabetes Guidelines
While the KDIGO 2022 guidelines recommend GLP-1 receptor agonists for patients with type 2 diabetes and CKD (particularly long-acting agents with cardiovascular benefits), they note that most GLP-1 RAs require no dose adjustment but have limited data in severe CKD. 2
The guidelines show that dulaglutide (another GLP-1 RA) can be used with eGFR >15 ml/min/1.73 m², and semaglutide requires no dose adjustment but has limited data for severe CKD. 2
Clinical Pitfalls to Avoid
Do not confuse the lack of need for dose adjustment with lack of need for monitoring—volume depletion from gastrointestinal side effects remains a significant risk that can worsen renal function. 1
Unlike metformin (which requires dose reduction at eGFR 30-44 ml/min/1.73 m² and discontinuation below 30) or exenatide extended-release (contraindicated below eGFR 45), tirzepatide has no such restrictions. 2
The half-life of tirzepatide is approximately 5 days, so in the event of overdosage or severe adverse reactions in patients with renal impairment, prolonged observation may be necessary. 1