Chronic kidney disease worsened heart failure severity but did not diminish tirzepatide benefits, though kidney function changes were hard to assess due to body composition shifts.
2xHigher heart failure event rate in patients with chronic kidney disease
What the researchers found
CKD doubled heart failure event rates, but tirzepatide benefits were consistent across kidney function levels. Creatinine-based and cystatin C-based eGFR gave discordant results.
Why it matters
Many HFpEF patients have CKD, and understanding drug-kidney interactions is essential for safe prescribing.
The numbers in context
Of 1,145 participants: 8.8% under 55, 23.3% aged 55-64, 42.4% aged 65-74, 25.5% aged 75+. KCCQ-CSS interaction P = 0.80. Body weight interaction P not significant. Treatment: 52 weeks.
How the study worked
Pre-specified analysis of the SUMMIT double-blind RCT with 731 patients enriched for CKD.
Who was studied
Adults with obesity-related HFpEF across four age groups (under 55 to 75+)
What this study cannot tell us
Sub-analysis of SUMMIT; not powered for CKD subgroup outcomes. Short-term renal function data.
How to read the evidence
Pre-specified sub-analysis of a high-quality RCT. Moderate evidence for CKD subgroup findings.
When this study was published
Published in 2025 from the SUMMIT trial.
The bigger picture
Weight-loss therapies create measurement challenges for kidney function tracking, requiring clinicians to use cystatin C-based estimates.
Questions still open
- Should cystatin C-based eGFR become standard for patients on GLP-1/GIP drugs?
- Does tirzepatide have direct renoprotective effects?
Common questions
Can patients with kidney disease take tirzepatide for heart failure?
Why are kidney tests unreliable during tirzepatide treatment?
Read the original research
Effects of semaglutide in obesity-related heart failure with preserved ejection fraction across the age spectrum: Findings from the STEP-HFpEF programme.
European journal of heart failure, 27(11), 2537-2543
Citation
Pandey, Ambarish; Moroney, Michael; Verma, Subodh; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Kitzman, Dalane W; Shah, Sanjiv J; Petrie, Mark C; Rönnbäck, Cecilia; Domdey, Anne; Rasmussen, Søren; Chinnakondepalli, Khaja M; Patel, Shachi; Kosiborod, Mikhail N. (2025). Effects of semaglutide in obesity-related heart failure with preserved ejection fraction across the age spectrum: Findings from the STEP-HFpEF programme.. European journal of heart failure, 27(11), 2537-2543. https://doi.org/10.1002/ejhf.70049