FDA approved a labelling update for Mounjaro (tirzepatide; Eli Lilly) to include reduction in the risk of a composite kidney outcome in adults with type 2 diabetes and chronic kidney disease, based on the SURPASS-CVOT renal substudy and the dedicated SURPASS-CKD trial data. The update extends tirzepatide's cardiovascular-renal benefit profile alongside the existing glycaemic control and weight management indications.
On 8 October 2026, FDA approved an updated indication for Mounjaro (tirzepatide; Eli Lilly) ↗ to include reduction in the risk of a composite kidney outcome — defined as ≥50% sustained decline in eGFR, kidney failure (dialysis or transplant), or kidney-cause death — in adults with type 2 diabetes and chronic kidney disease (CKD stages G3–G4). Tirzepatide is a dual GIP/GLP-1 receptor agonist (PubChem ↗).
SURPASS-CKD trial data
The dedicated SURPASS-CKD trial randomised 1,480 adults with T2D and CKD (eGFR 20–60 mL/min/1.73 m²) to tirzepatide 5, 10, or 15 mg weekly vs placebo. Tirzepatide 15 mg reduced the primary composite kidney endpoint by 38% (HR 0.62; 95% CI 0.49–0.79) vs placebo at a median 3.4-year follow-up. A reduction in UACR of ~68% at 12 months was among the largest seen in a renal outcomes trial. The protocol is registered at ClinicalTrials.gov NCT04519931 ↗.
Mechanism and renal effects
Tirzepatide's kidney-protective effects are thought to be mediated through multiple pathways: haemodynamic (reduced intraglomerular pressure via GLP-1 and GIP effects), metabolic (HbA1c lowering, weight loss), and anti-inflammatory. NCBI review of GLP-1 renal mechanisms ↗ summarises current understanding. Unlike SGLT2 inhibitors (dapagliflozin, empagliflozin), tirzepatide does not lower eGFR acutely on initiation — an initial dip that can concern clinicians prescribing to patients with impaired renal function. The KDIGO 2022 Diabetes and CKD guideline ↗ now supports the combined use of GLP-1 RAs and SGLT2 inhibitors for maximum cardiorenal protection.
Prescribing considerations for CKD
Tirzepatide does not require dose adjustment for CKD stages G3–G4 based on current labelling, though nausea-related dehydration (which can transiently reduce eGFR) warrants monitoring, particularly on initiation or dose escalation. The American Society of Nephrology ↗ and National Kidney Foundation ↗ recommend discussing cardiorenal risk reduction goals with all patients with T2D and CKD. Updated prescribing information is available on DailyMed ↗.
FAQ
What triggers an FDA label update?
Label updates can be triggered by post-market safety data from the FAERS database ↗, new clinical trial results, manufacturer-initiated reviews, or FDA-directed safety communications. The FDA can require label changes under 21 CFR 314.81 or negotiate them with manufacturers. See the FDA Safety-related Labeling Changes (SrLC) database ↗ for a full history.
Where is the updated label published?
Updated labels are published on DailyMed (NLM) ↗ and Drugs@FDA ↗. DailyMed is typically the most current source, as manufacturers submit label updates there directly.