Tirzepatide Improves Heart Failure Symptoms and Renal Function in People with Obesity, CKD

Milton Packer, MD

Photo courtesy of Heart Failure Society of America

In patients with heart failure with preserved ejection fraction (HFpEF) and obesity, the presence of chronic kidney disease (CKD) is associated with worse functional status and prognosis, but it does not diminish the clinical benefits of tirzepatide, according to findings presented at the 2025 American College of Cardiology Annual Scientific Sessions and simultaneously published in JACC.1

“The interplay of these three conditions identifies a patient population as exceptionally high risk, which means it’s a patient population that is exceptionally in need of treatments that work,” first author Milton Packer, MD, distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas, said in a press release.2 “This drug improves kidney function, obesity and HFpEF outcomes, thus improving all three elements that interact to create this syndrome.”

The analysis, derived from the SUMMIT trial, investigated the interplay of CKD and the effects of tirzepatide in 731 patients with obesity-related HFpEF (body mass index ≥30 kg/m²), enriched for the presence of CKD. Participants were randomized to receive either tirzepatide or placebo for a median of 104 weeks.1

Two primary objectives guided the analysis: to evaluate whether CKD influenced the clinical response to tirzepatide and to assess renal function changes, particularly in the context of differences between creatinine-based and cystatin C–based estimated glomerular filtration rate (eGFR) measurements.1

Baseline assessments showed that patients with CKD—defined by either creatinine or cystatin C criteria—had more severe heart failure, reflected by worse New York Heart Association functional class, lower Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS), shorter 6-minute walk distances, and higher levels of NT-proBNP and cardiac troponin T. These patients also faced a twofold increased risk of worsening heart failure events compared with those without CKD.1

Despite this greater disease burden, the relative benefit of tirzepatide on the primary composite outcome of cardiovascular death or worsening heart failure events, as well as improvements in KCCQ-CSS, quality of life, and functional capacity, was not diminished by CKD status. The absolute risk reduction in primary events was numerically higher among patients with CKD.1

Regarding renal function, baseline eGFR measured by cystatin C was approximately 9 mL/min/1.73 m² lower than that measured by creatinine, with substantial individual variability. At 52 weeks, tirzepatide was associated with improvements in eGFR using both methods, though discordance was observed. At 12 weeks, a decline in creatinine-based eGFR was noted with tirzepatide, but not with cystatin C–based eGFR. By week 52, cystatin C–based eGFR improved across all patients, while improvements in creatinine-based eGFR were limited to those with CKD.1

Investigators concluded that the combination of obesity, HFpEF, and CKD defines a high-risk phenotype, yet one that responds to tirzepatide treatment. However, they cautioned that changes in body composition may affect both creatinine and cystatin C levels, potentially skewing eGFR measurements in this population.1

References:

1. Packer M, Zile MR, Kramer CM, et al. Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial. J Am Coll Cardiol. Published online March 24, 2025. doi:10.1016/j.jacc.2025.03.009

2. Tirzepatide Benefits People with Obesity, Kidney Disease and Heart Failure. News release. American College of Cardiology. March 31, 2025. Accessed April 11, 2025. https://www.acc.org/About-ACC/Press-Releases/2025/03/31/13/01/Tirzepatide-Benefits-People-with-Obesity