Barry A. Borlaug, MD is a cardiologist in Rochester, Minnesota, affiliated with the Mayo Clinic.

Barry A. Borlaug, MD

Tirzepatide Effects Men and Women with HFpEF Equally, With Barry Borlaug, MD

Tirzepatide achieves consistent benefits across multiple domains of 

 heart failure with preserved ejection fraction (HFpEF), irrespective of sex, according to a secondary analysis of the phase 3 SUMMIT trial.

Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025

 by Barry Borlaug, MD, associate professor of medicine at Mayo Clinic, this analysis aimed to determine potential variance in treatment response among women with obesity-related HFpEF. The disease is famously represented differently between both sexes, with women exhibiting greater severity in several disease aspects.

 sat down with Borlaug to discuss the findings of the study, how they may implement HFpEF treatment, and whether this method should be explicated to other medications.

“We know that women tend to have more severe obesity and a higher percent body fat,” Borlaug told 

. “There are some important differences: they have smaller, stiffer hearts, and they have more abdominal visceral fat relative to women without HFpEF. There are lots of reasons why [tirzepatide] should behave a little bit differently.”

The original SUMMIT trial included both men and women ≥40 years old with chronic HF defined as New York Heart Association class II to IV, left ventricular ejection fraction of ≥50%, and a body mass index (BMI) of ≥30. Enrolled patients also had a 6-minute walk distance between 100 and 425 m and a Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) of ≤80.

Eligible patients were randomly assigned in a 1:1 ratio to either tirzepatide subcutaneously at 2.5 mg/week or placebo, in addition to usual therapy. Patients were stratified according to HF decompensation occurrence within 12 months before baseline, a history of type 2 diabetes (T2D), and BMI over or under 35.

Ultimately, SUMMIT screened 1494 patients, 731 of whom were assigned to either tirzepatide (n = 364) or placebo (n = 367). Cardiovascular or HF-related death occurred in 36 patients in the tirzepatide group versus 56 in the placebo group. Mean KCCQ-CSS increase was 19.5 points in the tirzepatide group and 12.7 in placebo.

This secondary analysis included 393 female and 338 male patients from the initial SUMMIT group. Average BMI was 39 kg/m

 among men. Baseline waist circumference was 116.9 cm in the female group versus 123 cm in the male group. Investigators saw more severe baseline HF in women with HFpEF, noting an inverse relation between eGFR and waist-to-height ratio in women (

 = 0.043). However, men displayed more cardiac remodeling and paracardiac fat.

Despite these differences, investigators found similar benefits with tirzepatide versus placebo between both sexes. Men experienced a 10.6% reduction in body weight (95% CI, -12.2 to -8.9) compared to a 12.5% reduction in women (95% CI, -14.2 to -10.8). Time to worsening HF or cardiovascular disease was 0.66 in women (95% CI, 0.38 to 1.18) versus 0.61 in men (95% CI, 0.33 to 1.13).

Borlaug also spoke on the importance of using similar study methods to analyze potential sex differences in other medications, outside of both HFpEF and cardiology in general.

“I think this is something we should be looking at in basically all trials,” Borlaug said. “It’s a very straightforward analysis. We know that women and men are different in many ways, so we want to make sure that benefits are similar in both sexes. We pre-specify them, obviously, and plan for them in the statistical analysis plan. But yes, I think this is something that should routinely be done to better understand sex differences in response to treatment.”

Borlaug B. Effects of Tirzepatide in Obesity-Related HFpEF by Sex: A Prespecified Secondary Analysis from the SUMMIT Trial. Presented at the Heart Failure Society of America Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.

Packer M, Zile MR, Kramer CM, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025;392(5):427-437. 

Videos

A prespecified secondary analysis revealed no difference in male and female patients’ responses to tirzepatide in obesity-related HFpEF.

Tirzepatide Affects Men and Women with HFpEF Equally, With Barry Borlaug, MD

Expert Perspectives: Top News in Heart Failure from HFSA Annual Scientific Meeting 2025

The Heart Failure Society of America Annual Scientific Meeting 2025,

 incorporating over 50 scientific sessions and hundreds of abstract presentations from leading researchers, saw a slew of exciting trial updates and insights from some of the best minds in cardiology.

During the conference, the editorial team at 

 sat down with several of these experts, collecting their thoughts on the most significant developments in 

’s approval of finerenone, the upcoming decision on aficamten, and the recent VICTOR, SUMMIT, and MAPLE- and ODYSSEY-HCM trials were highlighted.

The clinicians included in this summary are:

Ronald Witteles, MD, professor of cardiovascular medicine at Stanford University and co-director of the Stanford Amyloid Center and the Stanford Multidisciplinary Sarcoidosis Program

Barry Borlaug, MD, professor of cardiology at Mayo Clinic

Justin Ezekowitz, MD, professor of medicine at University of Alberta and cardiologist at the University of Alberta Hospital and Mazankowski Alberta Heart Institute

Ahmad Masri, MD, director of the Oregon Health & Science University Hypertrophic Cardiomyopathy Center and Knight Cardiovascular Institute Cardiac Amyloidosis Program

Javed Butler, MD, MPH, professor and chair of the department of medicine and Patrick H. Lehan Chair of Cardiovascular Research at the University of Mississippi Medical Center

Benjamin Hansen, MD, postdoctoral research fellow at the Department of Intensive Care at Copenhagen University Hospital - Rigshospitalet

Henri Roukoz, MD, associate professor of medicine, cardiovascular division, and section chief of electrophysiology, director of complex and congenital ablation at the University of Minnesota

Petra Mamic, MD, instructor of cardiovascular medicine at Stanford University Medicine

Stephen Greene, MD, cardiovascular disease fellow at Duke University Medical Center

Viet Le, DMSc, PA-C, associate professor of research at Intermountain Health

Milind Desai, MD, director of the center for hypertrophic cardiomyopathy and vice chair of education of the Heart Vascular Thoracic Institute at the Cleveland Clinic

I may be biased, but to me, ATTR amyloidosis is still the biggest story in heart failure. You’re talking about a disease that, a decade ago, most people hadn’t heard of. Maybe there would be one session every few years at the meetings, which was sparsely attended, but there was little interest, it was wildly underdiagnosed, and there were no therapies for it. Now we’re in an era where we realize this disease is not that rare, that if you look at the right patient populations, particularly older men with heart failure, thick hearts, and atrial fibrillation, you will pick up a lot of this. And it’s easy to diagnose; most patients can be diagnosed non-invasively. And now we have 3 FDA-approved treatments for ATTR 

, we have multiple other treatments approved for ATTR polyneuropathy, and multiple other agents in phase 3 trials. It is a super dynamic area, and it’s one that I think is particularly gratifying because it went from a fundamental understanding of the pathophysiology of the disease that led directly to the therapies. In the world of ATTR amyloidosis, the therapies have been designed to do exactly what they do, and in a rare thing in medicine, they pretty much all work.


The SUMMIT trial is probably the biggest news. It wasn’t a lot of events, it wasn’t a big trial, but it was a statistically significant improvement with a drug that was developed for weight loss, and it’s really ushering in a new era. HFpEF is a disease that’s driven by adiposity and everything that comes with that, such as visceral adiposity, pro-inflammatory and profibrotic effects, and many others. It’s opening the door for a lot of different drugs and potentially even devices that can target this cardiometabolic axis.


 2025 has been a pretty banner year for some trials: the VICTOR trial, being the largest recent clinical trial, has been quite important; the completion of DAPA-ACT, being the last real SGLT2 trial, showing that, when in combination with the meta-analysis, there is an advantage to starting those drugs early on. I think seeing the secondary analysis from some trials, such as the SUMMIT trial and the MRI of adipose tissue, is really interesting because it shows there’s a change in the structure and function of the myocardium that really is interesting. We’ve had so many great smaller trials as well, though, so it’s hard to pick one. There’s so much good stuff going on.


 Focusing on hypertrophic cardiomyopathy specifically, I think the 2 recent trials that were published, MAPLE-HCM and ODYSSEY-HCM, are really important findings in this space. MAPLE-HCM showed that beta blockers, as represented by metoprolol, are detrimental to patients with obstructive hypertrophic cardiomyopathy. This challenges a practice of 60-plus years of using beta blockers as first-line therapy. You don’t see reversals in approach frequently, because you don’t see these first-time agents challenged frequently. ODYSSEY-HCM, on the other hand, while it wasn’t a positive trial, showed that you have to be careful in your evaluation of patients with hypertrophic cardiomyopathy. You have to be mindful that you can’t just use 1 trial in a specific population and expand the drug treatment to other populations without investigation. This is a drug that was successful in obstructive hypertrophic cardiomyopathy with some safety issues that were managed and dealt with that wasn’t successful in non-obstructive HCM, and the safety signal was much worse. The trial wasn’t positive, but it reminded us that we have to be really careful when applying an extension of the current use of drugs, and we have to strive to stay with evidence-based medicine as much as we can with our newer therapies.


 The biggest story so far is that the field continues to move forward. We had a lot of positive data that has come out of either smaller primary studies or secondary analyses of larger studies with the obesity trials. That is becoming the solid, certified data that evidence generation needs, which has led to a lot of ongoing studies. The other is smaller studies that have shown that aldosterone modulation in ways other than MRA, like aldosterone synthase inhibitors, may be very helpful. And third, there’s a lot of compelling data that has come out about prevention of heart failure in high-risk populations.


 If I were to call out just one big news, it’s the role of vericiguat. I think that’s something of a hot topic right now, so I guess that’s something we really need to look further into to see its role in this population of well-treated outpatients with difficult-to-treat or advanced heart failure.


I would say how widely the SGLT2 inhibitors are being used and the increase in the indication to cover HFpEF patients. The second part is rhythm control and afib in heart failure, which is still a dominant thing from the EP standpoint.


This past year, we’ve had incredible studies published about gut microbiome in the context of heart failure, which have really put certain gut microbial metabolites on the map for their roles in heart failure. I think where we have come from 2024 to 2025 has really informed my research in a huge way.


There’s some things to pick from, but one thing that’s very notable is the FDA approval of finerenone as an evidence-based treatment for HFpEF, not just diabetic kidney disease anymore. The FINEARTS trial was presented last year, but FDA approval now really solidifies this in my mind that we have another pillar for HFpEF. SGLT2 inhibitors were the first definitively proven therapy for patients with HFpEF, and despite making up more than half of our heart failure population, we had no evidence-based therapy, no disease-modifying therapy to offer them. Now we have another therapy that I would argue strongly is definitively proven for improving hard clinical outcomes. I think we need to embrace that.

I’d also like to encourage people to think that it’s not an either-or when we talk about the “pillars of therapy,” and I don’t want to make the same mistakes that we made in HFrEF. We have multiple evidence-based therapies; you need to be willing to initiate them simultaneously and not get distracted with this specific medication sequence. People need both for prognosis comparable to cancer, not either-or.


GLP-1s are one of these unifying therapies across multiple diseases, and I think as we think back to 2025, we’re just having this confluence of heart failure from the diabetic space. Everyone is reporting clinical data trending towards benefit with GLP-1s. I think this is such a great jump-off point. So many different industry partners are looking into this, and before 2025, they were thinking about it. But now I think the community is much more aware. I look forward to seeing where those fit in the space of heart failure, but also in cardiovascular, kidney, and metabolic health.


I think the continued evolution of high-quality randomized controlled trial data in the context of cardiomyopathy, not just hypertrophic obstructive cardiomyopathy. Gene therapy is rapidly evolving, and you’re going to hear a lot about it. The other important thing is the utilization of novel artificial intelligence techniques to make early and precise diagnoses in these spaces. A rising tide lifts all boats, so they say; there’s a major tide that is lifting a lot of boats right now.

The quotes contained in this video summary were edited for clarity.

Editor's Note: Le reports disclosures with Pfizer, Novartis, Janssen, Idorsia, Amarin, and Lexicon. Greene reports disclosures with Amgen, Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, Corcept, and others. Butler reports disclosures with Abbott Laboratories, Amgen, Bristol-Myers Squibb, Cytokinetics, Medtronic, Merck, and others. Masri reports disclosures with Pfizer, Ionis Pharmaceuticals, AstraZeneca, Cytokinetics, BioMarin, Akros, and others. Desai reports disclosures with Bristol-Myers Squibb, Medtronic, Cytokinetics, Edgewise, Viz-Al, and Tenaya Therapeutics. Borlaug reports disclosures with Amgen, Novo Nordisk, Eli Lilly, Edwards LifeSciences, Boehringer Ingelheim, AstraZeneca, and others. Witteles reports disclosures with Pfizer, Alnylam Pharmaceuticals, Bridge Bio, Janssen, AstraZeneca, and Alexian Pharmaceuticals. Roukoz, Hansen, Mamic, and Ezekowitz report no disclosures.

US FDA Approves KERENDIA (finerenone) to Treat Patients with Heart Failure with Left Ventricular Ejection Fraction ≥40% Following Priority Review. Bayer. July 14, 2025. Accessed October 3, 2025. 

https://www.bayer.com/en/us/news-stories/fda-approves-kerendia

Reddy YNV, Butler J, Anstrom KJ, et al. Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial. Eur J Heart Fail. 2025;27(2):209-218. 

Packer M, Zile MR, Kramer CM, et al. Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial. J Am Coll Cardiol. 2025;85(18):1721-1735. 

Hegde SM, Wang X, Garcia-Pavia P, et al. Effect of Aficamten Compared With Metoprolol on Echocardiographic Measures in Symptomatic Obstructive Hypertrophic Cardiomyopathy: MAPLE-HCM. J Am Coll Cardiol. Published online August 27, 2025. 

Desai MY, Olivotto I, Abraham T, et al. Effects of Mavacamten on Cardiac Biomarkers in Nonobstructive Hypertrophic Cardiomyopathy: Insights From the ODYSSEY-HCM Trial. J Am Coll Cardiol. Published online August 25, 2025. 

This set of interviews collects perspectives from 11 leading clinicians in the heart failure field, cataloguing the biggest news from 2025.

Barry A. Borlaug, MD: Impact of Tirzepatide on Cardiorenal End-Organ Damage in HFpEF 

Tirzepatide lowered circulatory pressure-volume overload and reduced end-organ damage in the kidney and heart in patients with 

heart failure with preserved ejection fraction (HFpEF)

, according to data from the SUMMIT trial.

American Heart Association (AHA) Scientific Sessions 2024

, these data build upon the known benefit of tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist (GLP-1 RA), for the treatment of obesity-related HFpEF.

“I think it ties together a lot of the pathophysiologic components that we think are very important in obesity-related HFpEF, and tirzepatide seems to be working through many of these different pathways, some of them hemodynamic and volume-loading and [others] related to inflammation,” presenting investigator Barry A. Borlaug, MD, Mayo Clinic, told 

The double-blind SUMMIT trial randomized 731 individuals with NYHA Class II-IV heart failure, an EF of ≥50%, and body mass index (BMI) ≥30 kg/m2 to tirzepatide (n = 364) or placebo (n = 367). Tirzepatide was titrated to a maximum weekly tolerated dose of up to 15 mg subcutaneously.

For the analysis, Borlaug and colleagues collected data on blood pressure, anthropometrics, estimated plasma volume, and blood samples at baseline and 52 weeks, to determine biomarkers of cardiorenal function in all patients. Primary results from SUMMIT showed tirzepatide lowered the risk of cardiovascular death or worsening heart failure (hazard ratio [HR], 0.62; 95% CI, 0.41–0.95; 

Trial participants exhibited borderline hypertension (systolic blood pressure [SBP], ~128 mmHg), volume expansion (estimated plasma volume, ~3.3 L), chronic kidney disease (urine albumin/creatinine ratio [UACR], ~2.8 g/mol), and subclinical myocardial injury (troponin T, ~11 ng/L).

Compared with placebo, tirzepatide treatment reduced SBP by ~6 mmHg (95% CI, –8 to –4; 

<.001) at 24 weeks and by –5 mmHg (95% CI, –7 to –3; 

 <.001) at 52 weeks, respectively. Tirzepatide also decreased the estimated plasma volume by ~0.32 L (95% CI, –0.36 to –0.27; 

At the same time, tirzepatide achieved an increase in eGFR at 52 weeks (~1.85 ml/min/1.73 m2; 95% CI, 0.19–3.51; 

 = .029), decreases in microalbuminuria at 24 weeks (–25.0%; 95% CI, –36 to –13; 

 <.001) and 52 weeks (–15%; 95% CI, –28 to 0.1; 

 = .051), and a reduction in troponin T at 24 weeks (–9.8%; 95% CI, –16.0 to –3.3; 

 = .004) and 52 weeks (–10.4%; 95% CI, –16.7 to –3.6; 

“I think we need to be looking to use these drugs, these incretin-based drugs, more frequently, including tirzepatide, for the treatment of people with obesity-related HFpEF,” Borlaug told 

Disclosures: Borlaug reports relevant disclosures with Amgen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and others.

Borlaug BA. Effects of Tirzepatide on Cardiorenal End-Organ Damage in Heart Failure and Preserved Ejection Fraction: Insights from the SUMMIT trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.

Tirzepatide, a GLP-1 RA, demonstrated significant benefits in reducing circulatory pressure-volume overload and end-organ damage in patients with HFpEF and obesity, as shown in the SUMMIT trial. The trial, presented at the AHA Scientific Sessions 2024, involved 731 participants and revealed that tirzepatide lowered cardiovascular death risk and improved cardiorenal biomarkers. Notable improvements included reductions in systolic blood pressure, plasma volume, microalbuminuria, and troponin T levels, alongside an increase in eGFR. These findings suggest tirzepatide's potential in managing obesity-related HFpEF.

Barry A. Borlaug, MD describes the beneficial effect of tirzepatide on circulatory pressure-volume overload and end-organ damage in patients with HFpEF and obesity.

Barry A. Borlaug, MD

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