Weight loss drug Zepbound may reduce death risk from heart failure by 38%

• Heart failure is a serious condition that can often be a challenge to manage and researchers are trying to determine which medications can help it.
• The results of a recent study indicate that the drug tirzepatide may help decrease the risk for hospitalizations from heart failure, improve symptoms, and reduce the risk of death.
• The results indicate that tirzepatide, sold under the brand name Zepbound, might benefit individuals with heart failure with preserved ejection fraction.

Cardiovascular health is critical to the survival and health of the entire body. Heart failure occurs when the heart cannot pump blood effectively throughout the body. The condition can be detrimental to cardiovascular health outcomes.

Researchers have been interested in what strategies are most effective in helping people with heart failure.

The results of a recent phase three trial, shared by Eli Lilly who is the manifacturer of tirzepatide, suggest that the medication may be very helpful for specific individuals with heart failure.

The trial found that tirzepatide may help reduce hospitalizations from heart failure, reduce cardiovascular death by 38%, and improve physical function for people with heart failure with preserved ejection fraction.

While tirzepatide is used for managing type 2 diabetes under the brand name Mounjaro , it’s also approved by the FDA under the brand name Zepbound for weight management under certain conditions.

Challenges of heart failure with preserved ejection fraction

One type of heart failure is heart failure with preserved ejection fraction (HFpEF) . Ejection fraction is the amount of blood the heart’s lower chambers (called ventricles) pump out. If this amount is still above 50%, but the left ventricle stiffens, then it is deemed to be HFpEF. This type of heart failure can be challenging to diagnose .

Cheng-Han Chen, MD , board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, who was not involved in the study, explained more to Medical News Today :

“Congestive heart failure (CHF) is one of the most common categories of cardiovascular disease, accounting for a significant burden of morbidity and mortality in the population. It can significantly affect someone’s quality of life and functional capacity.”

“The subtype of CHF that has been the most challenging to diagnose and treat is known as ‘heart failure with preserved ejection fraction’ (HFpEF). Some challenges of this condition include an incomplete understanding of the pathophysiology behind the condition, a lack of a single diagnostic test for the condition, and a relative paucity of medications that can significantly improve this condition,” he said.

Thus, it would be highly beneficial for researchers to find more medications that can help manage this type of heart failure.

The ways tirzepatide improves heart health

As noted in the details reported on ClinicalTrials.gov , researchers of the current study wanted to examine the effects of tirzepatide in people with obesity and HFpEF.

This phase three, randomized, double-blind, placebo-controlled clinical trial was completed in July 2024 and included 731 participants aged forty and older. Some participants received a placebo, while others received tirzepatide. Ten different countries were involved in data collection, allowing for a diverse sample.

Researchers excluded participants with certain heart conditions, uncontrolled diabetes, and non-heart-related conditions that limited function. All participants were on stable doses of heart failure medications and had a body mass index of 30 or more.

One primary outcome was changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Scores (CSS). This assessment helps measure the effects of heart failure in people’s lives, looking at components like symptoms and physical limitations. The other primary outcome was the occurrence of cardiovascular death, other heart failure events, or both. Researchers also looked at a number of secondary outcomes, including weight loss and exercise capacity changes.

Eli Lilly and Company sponsored the study. The results found that tirezepatide was superior to the placebo. Tirzepatide decreased participants’ risks for heart failure hospitalizations and urgent visits, cardiovascular deaths, and increases in oral diuretic use by 38%.

Participants with and without type two diabetes who took tirzepatide also saw over a 15% body weight reduction compared to a 2.2% weight reduction among placebo participants. Participants taking tirzepatide also experienced improvements in exercise capacity and heart failure symptoms.

Richard Wright, MD , a board-certified cardiologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study, noted the following about the study results to Medical News Today :

“This is an important study that extends recent observations on how drugs that originally were developed for diabetes and obesity can exhibit important clinical benefits in cardiovascular disease. The condition of preserved ejection fraction is pervasive and troublesome, with few documented treatments that have shown persistent and significant improvement in patients with the condition. Tirzepatide now joins that short list.”

“These findings strongly support the concept that tirzepatide could emerge as a cornerstone therapy for heart failure – at least in those people with obesity, type 2 diabetes, and heart failure with a normal or near-normal ejection fraction. We eagerly await the full publication of the study results.”
— Richard Wright, MD

Can I be prescribed tirzepatide yet?

The primary limitation of the research is that the study results still need to be published. When the full study is published, more data will be available, including the limitations of the research.

In addition, this trial looked at a specific demographic: individuals with obesity and heart failure with preserved ejection fraction. Thus, future research can look at how the use of tirzepatide impacts additional groups.

It’s also slightly unclear if the study results are truly a direct effect of tirzepatide, so future research can also look at this component.

“The difficulty in understanding the cardiovascular benefits of tirzepatide resides mostly in the expected and substantial weight loss seen in the treated group, which by itself is known to improve the observed outcome metrics,” said Wright.

“It is impossible to clearly distinguish between weight-loss-dependent and weight-loss-independent (if any) benefits of the drug. To accurately determine whether it is the drug itself, and not just weight loss, that is the beneficial factor cannot be known until the drug is utilized as a treatment for heart failure in non-diabetics and those who are not considered to [have obesity],” he noted.

However, the results point to another medication that could be very useful in helping people with HFpEF, offering an additional treatment option.

“Heart failure is a very difficult disease to treat with over a million heart failure hospitalizations in the U.S. every year. Not only is this a huge economic burden for patients and the health care system, but it also leads to even worse heart failure symptoms or even death,” Majid Basit, MD , a cardiologist with Memorial Hermann, who was not involved in the study, told MNT .

“Drugs like tirzepatide may soon be included in heart failure algorithms to be used in conjunction with traditional heart failure medications. We will see more trials soon to show us where these new medications fit in the heart failure treatment algorithm.”
— Majid Basit, MD