Abstract: TH-PO1222
Acute Dip in eGFR in Patients Treated with Tirzepatide: A Post Hoc Analysis of Long-Term Clinical Trials of Tirzepatide Treatment
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Linetzky, Bruno, Eli Lilly and Company, Indianapolis, Indiana, United States
- Stefanski, Adam, Eli Lilly and Company, Indianapolis, Indiana, United States
- Jouravskaya, Irina, Eli Lilly and Company, Indianapolis, Indiana, United States
- Cao, Dachuang, Eli Lilly and Company, Indianapolis, Indiana, United States
- Wiese, Russell J, Eli Lilly and Company, Indianapolis, Indiana, United States
- Griffin, Ryan, Eli Lilly and Company, Indianapolis, Indiana, United States
- Pavo, Imre, Eli Lilly and Company, Indianapolis, Indiana, United States
- Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands
Background
Nephroprotective therapies generally reduce glomerular hyperfiltration by reducing glomerular pressure, which manifests clinically as an acute and reversible dip in eGFR. This post-hoc analysis evaluates the presence of a dip in eGFR in two long-term trials of tirzepatide (TZP) and subsequent effects on eGFR for participants with and without a dip by 12 weeks of treatment.
Methods
SURPASS-4 recruited adults with T2D randomized 1:1:1:3 to TZP 5:10:15mg or insulin glargine [iGlar] 100U/mL once-weekly for up to 104 weeks. The SURMOUNT-1 3-year study recruited adults with obesity or overweight and prediabetes randomized 1:1:1:1 to TZP 5:10:15mg or placebo (PBO) for 176 weeks. Participant groups were classified as having no decrease, a decrease of 0-10%, or a decrease of ≥10% from baseline to week-12 in creatinine-based eGFR (Cr-eGFR). A Chi-square test was used to compare the incidence of week-12 eGFR dip between treatment groups. Changes in Cr-eGFR over time (Cr-eGFR slope) were assessed from randomization to end of treatment using random effect mixed model with TZP doses pooled.
Results
The analyses included 1924 SURPASS-4 (TZP: 960; iGlar: 964) and 942 SURMOUNT-1 (TZP: 700; PBO: 242) participants. In SURPASS-4, a significantly greater proportion of participants in the TZP vs iGlar group exhibited a week-12 Cr-eGFR decrease (0-10% or ≥10%); p<0.001. The Cr-eGFR slope was smaller for TZP vs iGlar regardless of the presence or magnitude of the Cr-eGFR dip. In SURMOUNT-1 there were no significant differences in either the incidence of Cr-eGFR dip or Cr-eGFR slope per year among treatment groups.
Conclusion
These post-hoc analyses indicate a more frequent incidence of a dip in Cr-eGFR in TZP-treated (compared to iGlar-treated) participants with T2D. Furthermore, the presence of an acute dip in Cr-eGFR with TZP treatment was not associated with a more pronounced decline in kidney function.
Funding
- Commercial Support – Eli Lilly and Company