In a major breakthrough for cardiovascular medicine, new research has revealed that widely prescribed weight loss drugs can dramatically lower the risk of hospitalization and death among patients suffering from heart failure with preserved ejection fraction (HFpEF). The findings, published on September 1, 2025, in JAMA and unveiled at the European Society of Cardiology’s annual conference in Madrid, suggest that medications such as semaglutide and tirzepatide—originally developed for diabetes and obesity—could offer a lifeline to millions grappling with this challenging form of heart disease.
HFpEF, a condition where the heart’s pumping function remains intact but its muscle becomes too stiff to fill properly with blood, affects more than 30 million people worldwide, according to data cited by researchers at the Technical University of Munich (TUM). Despite its prevalence, treatment options for HFpEF remain limited, leaving patients and clinicians in search of more effective therapies.
The new study, led by a team from TUM in collaboration with Harvard Medical School and Mass General Brigham in Boston, analyzed real-world data from three large US insurance claims databases. This approach enabled the researchers to assess outcomes in a population of around 100,000 patients—nearly 20 times larger than those involved in traditional clinical trials. Such a vast dataset allowed for a more comprehensive understanding of how these drugs perform outside the tightly controlled environment of a clinical trial, reflecting the realities of everyday medical practice.
"Together with our colleagues at Harvard Medical School, we have created a solid evidence base for using these weight-loss medications in heart failure," said Professor Heribert Schunkert, Director of the Department of Cardiovascular Diseases at the TUM University Hospital German Heart Center, as reported by Science X. He added, "In patients with heart failure with preserved ejection fraction, both drugs have shown a clear protective effect that supports their use. Our analysis of around 100,000 patients provides a robust basis for reassessing indication expansion and new indication approval in heart failure."
The study’s focus was on two drugs: semaglutide (sold under the brand names Ozempic and Wegovy) and tirzepatide (marketed as Mounjaro). Both belong to a class of medications known as GLP-1 agonists, which mimic a hormone that helps regulate appetite and blood sugar. While their efficacy in promoting weight loss and controlling diabetes is well established, their potential cardiovascular benefits have only recently come to light.
According to the findings, patients taking semaglutide experienced a 42% reduction in the risk of being hospitalized for heart failure or dying prematurely, compared with those on a diabetes drug that had previously shown no effect on heart failure outcomes. Tirzepatide delivered even more striking results, reducing this risk by a remarkable 58%. These numbers represent a substantial leap forward in the quest to improve outcomes for people living with HFpEF.
Dr. Nils Krüger, lead author of the study and a resident physician at TUM University Hospital German Heart Center, emphasized the significance of these results. He stated, "Currently, HFpEF can be treated with a few drugs only. At the same time, an increasing number of patients suffer from obesity and diabetes, which further worsens outcomes. In Germany, heart failure is the leading cause for hospitalizations and a major driver of health care expenditure. Our study shows that these drugs are highly effective, which expands treatment options and could prevent many hospital admissions."
The study’s methodology was notable for its reliance on large-scale, anonymized health insurance data, a strategy that is gaining traction in medical research. As Professor Schunkert explained, "The future belongs to such data‑driven approaches—alongside traditional trials, they can help ensure that findings from basic research feed into patient care more quickly." This approach aligns with recent legislative changes in Germany, where the Health Data Utilization Act will make anonymized health insurance data more systematically available for research, while maintaining strict privacy protections.
At the European Society of Cardiology conference in Madrid, the findings were met with cautious optimism from experts in the field. Dr. Carlos Aguiar, vice-president of the European Society of Cardiology and a cardiology consultant at Hospital Santa Cruz in Carnaxide, Portugal, commented, "What this shows is that there is a benefit in using one of these two agents, semaglutide or tirzepatide, to reduce the risk of hospitalisation for heart failure or all-cause mortality." He further noted, "We thought that we actually might not really find a treatment that would work well for a significant proportion of these patients, and what’s been a good surprise is that these drugs that are working through weight loss, but possibly through other effects that go beyond weight loss, are potentially reducing the rates of hospitalisation and mortality in patients with heart failure."
Dr. Sonya Babu-Narayan, a consultant cardiologist and clinical director of the British Heart Foundation, also welcomed the results, saying, "These data add to the growing body of evidence supporting a role for weight loss drugs for patients living with both heart failure and obesity, to reduce hospital admissions and death. It’s crucial that eligible heart failure patients have the opportunity to be considered for these therapies, alongside other evidence-based heart failure medicines."
While the results are undeniably promising, both Dr. Aguiar and Dr. Babu-Narayan stressed the need for further research before these drugs can be recommended for all heart failure patients. The study’s authors echoed this sentiment, acknowledging that more evidence is required to fully understand the mechanisms at play and to determine which patients stand to benefit most.
Beyond heart failure, the study adds to a mounting body of evidence suggesting that GLP-1 agonists may help prevent or manage a range of cardiovascular conditions. In May, a separate trial found that semaglutide reduced the risk of heart attack, stroke, or death from cardiovascular disease by 20%, regardless of a patient’s initial weight or the amount of weight lost. These findings hint at benefits that may extend beyond weight control alone, perhaps involving improvements in blood sugar regulation, inflammation, or other metabolic factors.
As the medical community digests these new results, the implications for patient care could be profound. Heart failure remains a leading cause of hospitalization and a major contributor to health care costs, particularly in aging populations. The prospect of a widely available, well-tolerated medication that can significantly reduce the risk of hospitalization or early death is, as several experts noted, "good news." However, regulatory authorities and professional societies have urged caution, emphasizing the need for continued research and careful consideration before expanding the use of these drugs to new patient groups.
For now, the study stands as a testament to the power of big data and international collaboration in advancing medical knowledge. As health systems around the world grapple with the growing burden of heart failure, these findings offer a glimmer of hope—and a call to action for further research and thoughtful integration into clinical practice.
