March 31, 2025
2 min read
Key takeaways:
- The clinical benefits of tirzepatide in patients with HFpEF and obesity were consistent regardless of kidney function.
- The effect of tirzepatide on kidney function depends on how CKD is defined, researchers said.
CHICAGO — In patients with heart failure with preserved ejection fraction and obesity, tirzepatide improved clinical outcomes compared with placebo regardless of chronic kidney disease, according to new data from the SUMMIT trial.
As Healio previously reported, the main results of SUMMIT demonstrated that tirzepatide (Zepbound, Eli Lilly) reduced risk for CV death and worsening HF by 38% compared with placebo in patients with HFpEF and obesity. Milton Packer, MD, Distinguished Scholar in Cardiovascular Science at Baylor University Medical Center, presented new data stratified by presence or absence of chronic kidney disease at the American College of Cardiology Scientific Session. The results were simultaneously published in the Journal of the American College of Cardiology.
The clinical benefits of tirzepatide in patients with HFpEF and obesity were consistent regardless of kidney function. Image: Adobe Stock
“In SUMMIT, we focused on the triad of HFpEF, obesity and chronic kidney disease,” Packer said during a presentation. “One of the enrichment criteria [for clinical events] was the presence of an [estimated glomerular filtration rate] less than 70 mL/min/1.73m2.”
The researchers assessed CKD using both creatinine, by which 54% of the cohort met criteria for CKD, and cystatin C, by which 61% of the cohort met criteria for CKD, Packer said.
Compared with patients without CKD, those with CKD were older, more likely to have NYHA class III or IV HF, had a higher N-terminal pro-B type natriuretic peptide level, had worse 6-minute walk distance, had higher troponin levels and were more likely to experience the primary endpoint of CV death or worsening HF during the median follow-up period of 104 weeks, Packer said.
The treatment effect of tirzepatide was consistent regardless of CKD for the primary endpoint (P for interaction = .77), as well as for the 52-week secondary endpoints of change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score, 6-minute walk distance, EQ-5D-5L index, NYHA class, body weight and high-sensitivity C-reactive protein (P for interaction > .05 for all), Packer said.
“But of course, the people with CKD had greater risk, so there was a greater absolute risk reduction with tirzepatide in people with CKD,” Packer said.
For patients with CKD, tirzepatide prevented 3.6 primary outcome events for 100 patients treated in 1 year, compared with 1.6 in patients without CKD, according to the researchers.
Interestingly, the effect of tirzepatide on kidney function depended on how CKD was defined, Packer said.
“Tirzepatide is lowering the number of adipocytes, so it’s lowering the production of cystatin C independent of kidney function,” Packer said. “So [if eGFR is measured by cystatin C], you get an improvement with tirzepatide whether you do or do not have chronic kidney disease. But if you use eGFR by creatinine, you only get an improvement with tirzepatide in people with chronic kidney disease, and not in people without chronic kidney disease. Creatinine is not influenced by adipocytes, it’s influenced by skeletal muscle, and that is also affected by a GLP-1/GIP receptor agonist.”
What this means, Packer said, is that “long-term, tirzepatide improves kidney function, regardless of how you look at it, but the measurement of eGFR in patients with obesity receiving incretin-based drugs is likely to be skewed by the effects on fat and muscle mass and changes in body composition.”
Reference:
Perspective
This is a very sick population who have the morbidities of obesity and CKD. It is a very large group of patients, which may not be well understood outside of the HF field. This is a group that has not had good pharmacotherapy in the past.
This extremely well-done trial had positive results and will probably be practice-changing. Importantly, there were positive effects on patient-reported outcomes, and patients taking tirzepatide feel better. You don’t want to live longer if you don’t feel good.
This population is hard to treat. First, we have to address decongestion and BP control. Then there are a lot of mobility issues. CKD limits some of the therapies we have for these problems. We can use GLP-1 receptor agonists to help with obesity in some of these patients, but not all. It can be hard to assess why people can’t move. I ask my patients what slows them down more, shortness of breath or problems with their legs, and sometimes they don’t know. This is a very deconditioned population, and we need to try every therapy we can, including things like physical therapy and cardiac rehabilitation.
Mary Norine Walsh, MD, MACC
Medical Director, Heart Failure and Cardiac Transplantation Programs
Ascension St. Vincent Heart Center, Indianapolis
Past President, American College of Cardiology
Disclosures: Walsh reports no relevant financial disclosures.
Sources/Disclosures
Collapse
Packer M, et al. Featured clinical research IV. Presented at: American College of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid meeting).
Disclosures:
The study was funded by Eli Lilly. Packer reports consulting for 89bio, AbbVie, Actavis, Altimmune, Alnylam, Amarin, Amgen, Ardelyx, ARMGO, AstraZeneca, Attralus, Biopeutics, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Eli Lilly, Imara, Medtronic, Moderna, Novartis, Pharmacocosmos, Reata, Regeneron, Roche and Salamandr. Please see the study for all other authors’ relevant financial disclosures.