Tirzepatide, a medication approved for treating obesity and Type 2 diabetes, demonstrated significant improvements in kidney function and cardiovascular health among patients suffering from obesity and heart failure with preserved ejection fraction (HFpEF), according to new clinical research presented at the American College of Cardiology’s Annual Scientific Session (ACC.25) and published in the Journal of the American College of Cardiology (JACC).
The study, which analyzed data from the SUMMIT trial, focused on patients with a combination of obesity, chronic kidney disease, and HFpEF—three interrelated conditions known to result in poor patient outcomes. While the overall rate of cardiovascular death or worsening heart failure was higher in the 60% of participants who also had chronic kidney disease, tirzepatide reduced the risk of the primary endpoint similarly for both those with and without kidney disease.
Addressing a Critical Unmet Need
Dr. Milton Packer, the study’s first author and Distinguished Scholar in Cardiovascular Science at Baylor University Medical Center, emphasized the significance of these findings, noting the high-risk nature of patients with these three conditions. “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,” Packer said. “This drug improves kidney function, obesity, and HFpEF outcomes, thus improving all three elements that interact to create this syndrome.”
HFpEF, which occurs when the heart muscle becomes stiff and unable to properly accommodate blood, and chronic kidney disease, in which the kidneys fail to filter waste effectively, both worsen over time. Tirzepatide works by targeting two receptors to reduce fat cell size, thereby improving heart and kidney health by shrinking enlarged fat cells.
Trial Design and Results
The SUMMIT trial enrolled 731 patients with HFpEF and a body mass index of 30 kg/m² or higher, half of whom were given tirzepatide and the other half a placebo. Notably, 60% of participants also had chronic kidney disease, with neither patients nor clinicians knowing which treatment was administered.
At one year, patients taking tirzepatide showed a 38% reduction in cardiovascular death or worsening heart failure compared with the placebo group. Additionally, tirzepatide participants demonstrated a significant improvement in heart failure severity, measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), which assesses heart failure symptoms.
Both primary endpoints showed similar improvements in patients with and without chronic kidney disease, although those with kidney disease generally faced worse outcomes across multiple metrics, such as more severe heart failure symptoms and a doubled risk of worsening heart failure.
Improvements in Kidney Function
In addition to cardiovascular benefits, tirzepatide also improved kidney function. Researchers assessed kidney function using creatinine and cystatin C levels at 12, 24, and 52 weeks. While results varied slightly over time, tirzepatide showed consistent improvement in kidney function markers compared to placebo, suggesting the drug’s positive impact on kidney health.
Dr. Packer highlighted that most patients with obesity, HFpEF, and chronic kidney disease currently have no effective treatments available. He expressed optimism about the potential for tirzepatide to provide a much-needed therapeutic option for this vulnerable patient population.
Future Insights and Study Continuation
The researchers plan to continue analyzing data from the SUMMIT trial to further understand the molecular mechanisms behind the interaction of obesity, kidney disease, and heart failure. The study was funded by Eli Lilly and Company.
These promising findings suggest that tirzepatide could become a valuable tool in treating patients with this complex and high-risk combination of conditions. The study, published simultaneously with its presentation at ACC.25, represents a significant step forward in the treatment of obesity-related heart and kidney diseases.
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