SUMMIT: Tirzepatide benefits people with obesity, kidney disease and heart failure

Tirzepatide improves kidney function and cardiovascular outcomes among patients with obesity and heart failure with preserved ejection fraction (HFpEF) compared with placebo at one year, according to the outcomes of the SUMMIT Trial presented at the American College of Cardiology's Annual Scientific Session.

The overall rate of cardiovascular death or worsening heart failure, the trial's primary endpoint, was higher in the 60% of study participants who also had chronic kidney disease. However, tirzepatide reduced the risk of the primary endpoint to a similar degree in patients with and without kidney disease.

In the analysis of data from the SUMMIT trial, researchers focused on patients with obesity, chronic kidney disease and HFpEF because they commonly have interacting root causes and are associated with poor outcomes, indicating a significant unmet need.

"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," said Dr Milton Packer, Distinguished Scholar in Cardiovascular Science at Baylor University Medical Center in Dallas and the study's first author. "This drug improves kidney function, obesity and HFpEF outcomes, thus improving all three elements that interact to create this syndrome."

Previous studies have shown improved kidney function with other drugs in the same class, but this trial is the first to assess tirzepatide's impact on kidney and cardiovascular outcomes in people with obesity, chronic kidney disease and HFpEF.

The SUMMIT trial enrolled 731 patients with HFpEF and a body mass index of 30 m2/kg or higher. About 60% of the study participants also had chronic kidney disease. Half were randomly assigned to receive tirzepatide and half received a placebo. Neither patients nor their clinicians were aware of which regimen they had been assigned.

At one year, patients taking tirzepatide had a 38% lower rate of cardiovascular death or worsening heart failure (defined as worsening heart failure symptoms in addition to hospitalization or the intensification of diuretic medications) compared with the placebo group. Participants taking tirzepatide also had a better average Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) than the placebo group, showing a significant improvement in terms of the study's second primary endpoint, a measure of heart failure severity.

For both of these primary endpoints, researchers observed similar improvement with tirzepatide in patients with and without chronic kidney disease. Overall, participants with chronic kidney disease faced poorer outcomes across multiple metrics compared to participants without chronic kidney disease, experiencing more severe heart failure symptoms on average and seeing twice the risk of worsening heart failure during the study.

The researchers used two strategies for assessing kidney function, measuring creatinine and cystatin C at 12, 24 and 52 weeks. Ultimately, participants taking tirzepatide showed significant improvements over those taking placebo in terms of both markers of kidney function, although the results showed different patterns over time and among different patient groups.

"Most patients with obesity who have HFpEF and chronic kidney disease are not getting any effective treatment," Packer said. "We were very pleased to see the improvement in kidney function, which paralleled the favourable effects on the heart and on obesity."

Researchers said that both creatinine and cystatin C levels can be affected by factors such as obesity and skeletal muscle mass. Despite this potential confounder, the agreement between the two measurements in terms of the direction of change among study groups offers confirmation of the positive impact of tirzepatide on kidney functioning, Packer said.

The researchers plan to continue to analyse data from the SUMMIT trial for further insights into the molecular mechanisms that contribute to the interplay between obesity, kidney disease and heart failure.

The findings were also reported in the paper, ‘Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial’, published in the Journal of the American College of Cardiology. To access this paper, please click here