Abstract: FR-OR114
Prognostic Significance of eGFR Change at Week 12 on Kidney Outcomes Associated with Semaglutide Use in the FLOW Trial
Session Information
- Late-Breaking Research Orals: AKI, CKD, CKM, and More
October 23, 2026 | Location: Four Seasons Ballroom 2, Convention Center
Abstract Time: 05:42 PM - 05:54 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Friedman, Allon N., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Tuttle, Katherine R., University of Washington School of Medicine, Seattle, Washington, United States
- Mahaffey, Kenneth W., Stanford University School of Medicine, Palo Alto, California, United States
- Pratley, Richard E., AdventHealth Translational Research Institute, Orlando, Florida, United States
- Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Bax, Willem A., Northwest Clinics, Alkmaar, Netherlands
- Bellary, Srikanth, Aston University and University Hospitals Birmingham, Birmingham, United Kingdom
- Charytan, David M., New York University Grossman School of Medicine, New York, New York, United States
- Gorriz, Jose L., Hospital Clíníco Universitario, Universitat de València, Valencia, Spain
- Ji, Linong, Peking University People's Hospital, Beijing, China
- Pugliese, Giuseppe, Sapienza University of Rome, Rome, Italy
- Rayner, Brian, University of Cape Town, Cape Town, South Africa
- Schmieder, Roland E., University Hospital Erlangen, Erlangen, Germany
- Boesgaard, Trine Wellov, Novo Nordisk A/S, Søborg, Denmark
- Priyadarshini, Prachi, Novo Nordisk Global Business Services, Bengaluru, India
- Rasmussen, Soren, Novo Nordisk A/S, Søborg, Denmark
- Cherney, David, University of Toronto, Toronto, Ontario, Canada
Background
Kidney-protective therapies (renin-angiotensin-aldosterone system inhibitors, sodium–glucose cotransporter-2 inhibitors, and mineralocorticoid receptor antagonists) often induce an early hemodynamically mediated eGFR decline associated with long-term kidney protection. In this post hoc analysis of the phase 3 FLOW trial with semaglutide in people with T2D and CKD, we investigated the prognostic significance of early changes in eGFR at week (wk) 12 on the primary kidney outcome (persistent eGFR <15 mL/min/1.73 m2 or ≥50% reduction in eGFR, initiation of chronic KRT, or kidney/cardiovascular death).
Methods
Changes in eGFR from baseline (BL) to wk 12 in the semaglutide (n=1767) and placebo (n=1766) arms were estimated by a mixed model for repeated measures. The association of eGFR change from BL to wk 12 with predicted primary kidney event rate at wk 104 was assessed by Cox proportional hazards model with natural cubic spline.
Results
Mean (SE) eGFR change from BL to wk 12 was -1.09 (0.19) mL/min/1.73 m2 for semaglutide (placebo: -1.05 [0.19] mL/min/1.73 m2; Figure; A). In both arms, predicted primary kidney event rate was lowest with the least eGFR change at wk 12. With semaglutide, the predicted event rate rose slowly as eGFR change approached 0 mL/min/1.73 m2 and increased more rapidly with decline in eGFR (Figure; B). Placebo showed a similar pattern with higher event rates with greater magnitude of eGFR decline at wk 12. Results were consistent using acute eGFR slope/year or adjusting for albuminuria.
Conclusion
A decline in eGFR with semaglutide at wk 12 was associated with higher predicted primary kidney event rates, differing from effects with other classes of kidney-protective therapies. Further study without post-randomization bias is merited.
Funding
- Commercial Support – Funding: The FLOW trial was funded by Novo Nordisk A/S and is registered with ClinicalTrials.gov (NCT03819153).