Published online Jun 18, 2026. doi: 10.13105/wjma.v14.i2.119849
Revised: March 8, 2026
Accepted: March 19, 2026
Published online: June 18, 2026
Processing time: 125 Days and 8.7 Hours
Obesity-related heart failure with preserved ejection fraction (HFpEF) is highly prevalent, symptomatically disabling, and lacks clearly disease-modifying phar
To systematically evaluate the efficacy and safety of GLP-1–based incretin ago
PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, and Web of Science were searched from inception to October 2025 for randomized controlled trials (RCT) evaluating GLP-1–based incretin agonist therapy in adults with HFpEF and obe
Three RCTs (n = 1876) were included in quantitative synthesis: STEP-HFpEF (n = 529), STEP-HFpEF DM (n = 616), and SUMMIT (n = 731). GLP-1-based incretin agonist therapy significantly improved health status, with a pooled increase in KCCQ-CSS of +7.33 points [95% confidence interval (CI): 5.84 to 8.82; I² = 0%]. Substantial weight loss was observed, with a pooled reduction of -9.56 percentage points (95%CI: -12.15 to -6.97; I² = 58%). Tirzepatide sig
GLP-1-based incretin agonists produce clinically meaningful improvements in symptoms, functional capacity, and body weight in patients with obesity-related HFpEF, with consistent benefit across trials and acceptable safety. Meta-analysis confirms robust improvement in health status and substantial weight reduction, supporting this therapeutic class as a promising disease-modifying strategy for this high-risk HFpEF phenotype. Tirzepatide additionally reduced hard CV outcomes, providing proof of concept that targeting obesity can favorably alter HFpEF disease course.
Core Tip: Glucagon-like peptide-1 (GLP)-1-based incretin agonists, including semaglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, produce consistent and clinically meaningful improvements in symptoms, functional capacity, and body weight in patients with obesity-related heart failure with preserved ejection fraction. Tirzepatide additionally reduced the composite of cardiovascular death or worsening heart failure events, establishing weight-centric pharmacotherapy as a promising disease-modifying strategy for this high-risk and previously treatment-resistant phenotype.
- Citation: Al Mashtoub E, Hteit A, Bedran A, Al Banna J, El Hachem C, Obeid N, Msheik M, Tlais M, Abdulaal R. Glucagon-like peptide-1-based incretin agonists in obesity-related heart failure with preserved ejection fraction: A systematic review and meta-analysis. World J Meta-Anal 2026; 14(2): 119849
- URL: https://www.wjgnet.com/2308-3840/full/v14/i2/119849.htm
- DOI: https://dx.doi.org/10.13105/wjma.v14.i2.119849
Heart failure with preserved ejection fraction (HFpEF) in the setting of obesity represents a distinct heart failure (HF) phenotype with high prevalence and unmet therapeutic needs[1]. Approximately 60% of HFpEF patients have coexisting obesity, which is associated with worse symptoms, poorer exercise capacity, and higher risk of HF hospitalization compared to non-obese HFpEF[1]. Weight loss and metabolic modulation have therefore emerged as promising targets in this “obese HFpEF” phenotype. Glucagon-like peptide-1 (GLP)-1-based incretin agonists-originally developed for type 2 diabetes and now widely used for obesity management-produce significant weight loss, reduce systemic inflammation, and improve endothelial function[2]. Given these benefits, GLP-1 receptor agonists (RAs) (e.g. semaglutide, liraglutide, and the dual agonist tirzepatide) have been investigated as a novel therapy for HFpEF in patients with obesity[2]. Recently, landmark trials such as STEP-HFpEF (with semaglutide) and SUMMIT (with tirzepatide) have reported en
This review was conducted and reported in accordance with the PRISMA 2020 statement. The review protocol was developed a priori; however, PROSPERO registration was not undertaken.
A systematic literature search was conducted in PubMed/MEDLINE, EMBASE, CENTRAL, and Web of Science from database inception to October 31, 2025. The search was restricted to human studies with no language restriction applied. An RCT filter (Cochrane Highly Sensitive Search Strategy) was applied in PubMed/MEDLINE; equivalent validated filters were used in other databases. The complete Boolean search strings, including all MeSH/Emtree terms, free-text synonyms, applied filters, and date limits for each database, are provided in Supplementary material. Briefly, the search strategy combined terms related to heart failure with preserved ejection fraction and GLP-1 RAs, including: “heart failure with preserved ejection fraction”, “HFpEF”, “obesity”, “GLP-1 receptor agonist”, “semaglutide”, “tirzepatide”, and related keywords. Reference lists of included studies and relevant reviews were manually screened to identify additional eligible trials. ClinicalTrials.gov was also searched to identify completed or ongoing trials.
Two reviewers (Bedran A and Hteit A) independently screened titles and abstracts for eligibility. Full texts of potentially relevant articles were subsequently assessed. Discrepancies were resolved by consensus, with adjudication by a third reviewer (Msheik M) when necessary. Studies were included if they met predefined criteria regarding population (adults with HFpEF and obesity), intervention (GLP-1 RAs or dual GIP/GLP-1 RAs), comparator (placebo or standard care), and outcomes (clinical events, exercise capacity, quality of life, or weight change). For the purposes of this review, HFpEF was required to be defined by the presence of symptoms and/or signs of HF, left ventricular (LV) ejection fraction ≥ 45%, and objective evidence of diastolic dysfunction or elevated left heart filling pressures-including elevated natriuretic peptides (BNP or NT-proBNP above guideline-defined thresholds), imaging evidence of structural heart disease (left atrial enlargement or LV hypertrophy), or invasive hemodynamic confirmation where reported. Studies relying solely on body mass index (BMI) ≥ 30 without additional HFpEF diagnostic confirmation were excluded. The study selection process is summarized in a PRISMA flow diagram (Figure 1).
Two reviewers independently extracted data using a standardized form. Extracted items included study design, setting, sample size, follow-up duration, participant characteristics [age, sex, BMI, LV ejection fraction (LVEF)], intervention details (agent, dose, titration), and outcomes [Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS)], 6-minute walk distance (6MWD), body weight change, HF hospitalization, cardiovascular (CV) death, biomarkers, and adverse events. Discrepancies were resolved by consensus.
Risk of bias for randomized trials was assessed independently by two reviewers using the Cochrane Risk of Bias 2 tool across five domains (randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result). Each domain and the overall risk were judged as low risk, some concerns, or high risk. Given that KCCQ-CSS is a patient-reported outcome, and that the prominent gastrointestinal side effects and marked weight loss associated with GLP-1-based therapy may allow participants to infer treatment allocation (functional unblinding), the domains of “measurement of the outcome” and “deviations from intended interventions” were assessed with particular scrutiny for the potential for performance and detection bias in subjective outcomes. A summary of risk-of-bias judgments is provided in Figure 2.
Where sufficient homogeneity existed, quantitative synthesis was performed using random-effects meta-analysis. Continuous outcomes were pooled using mean differences with 95% confidence intervals (CI). Time-to-event outcomes were summarized using hazard ratios with 95%CI. Binary (dichotomous) outcomes were summarized using risk ratios or odds ratios, as appropriate. Heterogeneity was assessed using the I² statistic, with values > 50% indicating substantial heterogeneity. Meta-analyses were conducted using RevMan version 5.4. Primary pooled outcomes included change in KCCQ-CSS and percentage body weight reduction. Sensitivity analyses were performed by excluding individual trials sequentially.
Primary outcome for quantitative synthesis was change in KCCQ-CSS. Secondary pooled outcome was percentage change in body weight. HF hospitalization and exercise capacity were synthesized descriptively due to differences in reporting across trials.
Publication bias assessment was not performed due to the small number of included trials.
Eight key publications (2023-2025) were included, comprising three primary RCTs and multiple secondary or pooled analyses. These studies evaluated the GLP-1-based incretin agonists semaglutide (a GLP-1 RA) and tirzepatide (a dual GIP/GLP-1 RA) in HFpEF patients with obesity. The main characteristics and findings are summarized below.
Overall risk of bias across the included RCTs was low to moderate. All studies demonstrated low risk of bias for randomization, missing outcome data, and selective reporting. Some concerns were identified in the SUMMIT trial regarding deviations from intended interventions due to higher treatment discontinuation related to gastrointestinal adverse effects. Additionally, for the primary patient-reported outcome (KCCQ-CSS), “some concerns” were noted across all three trials in the domains of “measurement of the outcome” and “deviations from intended interventions”, owing to the potential for functional unblinding: The characteristic gastrointestinal side effects and substantial visible weight loss associated with GLP-1-based therapy may allow participants to infer treatment allocation, potentially influencing subjective self-reported outcomes. A summary of risk of bias assessments is presented in Figure 2.
Random-effects meta-analysis demonstrated significant and consistent improvement in health status with GLP-1-based incretin agonist therapy. Pooled analysis across three RCTs showed a mean increase in KCCQ-CSS of +7.33 points (95%CI: 5.84-8.82; I² = 0%) compared with placebo (Figure 3A). GLP-1–based therapies also produced substantial body weight reduction, with a pooled mean difference of -9.56 percentage points (95%CI: -12.15 to -6.97; I² = 58%) (Figure 3B). The primary composite endpoint of CV death or worsening HF event (including HF hospitalizations and urgent HF visits) was significantly reduced in the SUMMIT trial with tirzepatide, while semaglutide trials demonstrated consistent favorable trends in hospitalization outcomes; however, HF event outcomes were not pooled across trials due to differences in endpoint definitions and reporting (SUMMIT used a time-to-event composite of CV death or worsening HF event, whereas the STEP-HFpEF trials used hierarchical composite outcomes). Sensitivity analyses excluding each trial sequentially did not materially alter the pooled estimates.
STEP-HFpEF trial (Semaglutide 2.4 mg vs Placebo, 52 weeks): This multinational RCT enrolled 529 patients with HFpEF (LVEF ≥ 45%) and BMI ≥ 30. Semaglutide led to a clinically significant improvement in symptoms and physical limitations (KCCQ-CSS) and in exercise capacity, along with dramatic weight loss[3]. Specifically, KCCQ-CSS increased by +16.6 points from baseline with semaglutide vs +8.7 with placebo (between-group difference approximately +7.8 points, P < 0.001), indicating markedly better quality of life[3]. Body weight fell by approximately 13.3% on semaglutide vs 2.6% on placebo (-10.7% difference, P < 0.001)[3]. Exercise capacity improved as reflected by a +21.5 m increase in 6MWD with semaglutide vs +1.2 m with placebo (approximately +20 m, P < 0.001)[3]. In a hierarchical composite outcome (death, HF hospitalization, and change in KCCQ-CSS and 6MWD), semaglutide-treated patients had significantly better overall clinical status (win ratio 1.72, P < 0.001)[3]. Inflammatory biomarker levels also improved [C-reactive protein (CRP) reduced by 44% vs 7% with placebo, P < 0.001][3]. Notably, safety was excellent-only 13.3% of semaglutide patients had serious adverse events, vs 26.7% with placebo[3]. This reflects fewer HF decompensation events in the treatment arm, as semaglutide recipients actually experienced fewer serious adverse events than controls in this HFpEF trial[3].
STEP-HFpEF DM trial (Semaglutide vs Placebo in HFpEF with type 2 diabetes): A parallel RCT of 616 HFpEF patients with obesity and diabetes showed broadly consistent benefits[4]. At 52 weeks, semaglutide improved KCCQ-CSS by +13.7 points vs +6.4 with placebo (approximately +7.3 point difference, P < 0.001)[4], and induced weight loss of approximately 9.8% vs 3.4% with placebo (-6.4% difference, P < 0.001)[4]. The 6MWD gain was more modest in this diabetic cohort (+14 m vs placebo, P < 0.01) but still significant[4]. A hierarchical clinical composite again favored semaglutide (win ratio 1.58, P < 0.001)[4]. Importantly, there were fewer serious adverse events in the semaglutide group (17.7% vs 28.8%, similar to the non-diabetic trial)[4], indicating consistent safety and potential HF hospitalization reduction. Thus, even in HFpEF patients with coexisting diabetes-who tend to have more comorbidities-GLP-1 RA therapy produced substantial weight reduction and symptomatic improvement[4].
Pooled analysis of Semaglutide HFpEF trials: Butler et al[5] reported a prespecified pooled patient-level analysis of the above two STEP-HFpEF trials (total n = 1145). This combined analysis confirmed that semaglutide was superior to placebo in improving HFpEF symptoms (KCCQ) and physical function (6MWD) and in reducing body weight[5]. The benefits were consistent across all tested subgroups, including age, sex, baseline BMI class, diabetes status, and NT-proBNP level[5]. Notably, semaglutide-treated patients had approximately half the number of serious adverse events compared to placebo (161 vs 301 events) across the pooled population[5], reinforcing that improved HF status translated into fewer hospitalizations or urgent visits. In summary, semaglutide yielded robust and homogeneous improvements in obesity-related HFpEF, without evidence of any subgroup harm[5]. This positions weight-loss therapy with GLP-1 RA as a disease-modifying strategy in this HFpEF phenotype.
STEP-HFpEF subgroup and mechanistic analyses: Further secondary analyses have explored how GLP-1 RA therapy achieves these benefits. A prespecified analysis by obesity class found that semaglutide’s effects on symptoms and function were uniformly positive across BMI categories (30-34.9, 35-39.9, and ≥ 40), with no attenuation of benefit in more severe obesity[1]. In fact, greater weight loss with semaglutide was correlated with greater improvements in KCCQ and 6MWD, implying that the magnitude of HF benefit was directly related to weight reduction[1]. Semaglutide-mediated weight loss (-10% or more) produced incremental gains in exercise capacity and quality of life[1]. These findings support intentional weight loss via GLP-1 RA as a key therapeutic mechanism in obese HFpEF[1]. In terms of cardiac structure, an echocardiographic substudy reported that semaglutide significantly reduced left atrial volume and improved diastolic function (E/e′ ratio) compared to placebo[2], suggesting a reverse remodeling effect that may underlie the clinical improvements.
SUMMIT trial (Tirzepatide 15 mg vs Placebo, median 2-year follow-up): The SUMMIT trial investigated tirzepatide, a dual GIP/GLP-1 RA, in 731 patients with HFpEF (EF ≥ 50%) and obesity. This longer-duration outcomes trial was pivotal in assessing hard clinical endpoints. Tirzepatide therapy led to a 38% relative risk reduction in the primary composite endpoint of CV death or worsening HF event (including HF hospitalizations and urgent HF visits) vs placebo (9.9% vs 15.3% event rate; hazard ratio 0.62, 95%CI: 0.41-0.95, P = 0.026)[6]. As a component of this composite, HF hospitalization was halved (8.0% vs 14.2%, HR approximately 0.54)[6], while CV death rates were low and not statistically different between groups[6]. In parallel, tirzepatide produced substantial symptomatic and functional gains-at 52 weeks, KCCQ-CSS improved by +19.5 points on tirzepatide vs +12.7 on placebo (between-group +6.9 points, P < 0.001)[6], closely mirroring the magnitude seen with semaglutide. Weight loss was marked (mean approximately 11%-12% reduction with tirzepatide) and was accompanied by improvements in 6MWD and biomarkers (inflammation and natriuretic peptides) as detailed in secondary analyses[7].
Safety: Tirzepatide’s known side effect of gastrointestinal discomfort was evident, with slightly higher drug discontinuation due to adverse events (6.3% vs 1.4% placebo)[6]. However, overall serious adverse event rates were lower with tirzepatide, reflecting fewer HF events. The trial concluded that in obese HFpEF patients, tirzepatide significantly reduces HF morbidity and improves health-related quality of life[6]. This was the first RCT to demonstrate a morbidity/mortality benefit in HFpEF through a weight-centric approach.
Mechanistic insights (tirzepatide secondary analyses): Beyond clinical endpoints, SUMMIT provided insight into physiological changes with tirzepatide in HFpEF. A cardiac magnetic resonance imaging substudy showed tirzepatide significantly reduced LV mass (by approximately 11 g vs placebo, P = 0.004) and reduced cardiac adipose tissue volume[8]. These structural benefits paralleled the degree of weight loss and likely contributed to improved diastolic function and fewer HF events[8]. Additionally, a secondary analysis by Borlaug et al[7] noted that tirzepatide lowered systemic blood pressure (approximately 5 mmHg), reduced plasma volume (-0.58 L), and markedly decreased inflammation (-37% CRP) compared to placebo. Tirzepatide also showed renal benefits (estimated glomerular filtration rate increase, less albuminuria) suggestive of cardio-renal stress relief[7]. Collectively, these findings indicate that tirzepatide favorably remodels the hemodynamic and metabolic milieu in obese HFpEF-lowering preload/afterload, reducing LV hypertrophy, and attenuating myocardial injury biomarkers[7]. Such multi-faceted improvements help explain the substantial clinical benefits observed with tirzepatide.
All included studies consistently demonstrate that GLP-1 RAs confer meaningful clinical benefits in HFpEF patients with obesity. Key efficacy outcomes are summarized as follows.
Symptoms and quality of life: Both semaglutide and tirzepatide produced large improvements in HF-specific health status (KCCQ-CSS gains of approximately 7-8 points vs placebo)[3,6]. These exceed the ≥ 5-point difference often considered clinically important in KCCQ, indicating patients felt significantly better. In many cases, patients on GLP-1-based incretin agonist therapy improved by one New York Heart Association Functional Classification (NYHA) functional class or more[2].
Exercise capacity: Trials uniformly reported improved exercise tolerance with GLP-1-based incretin agonists. 6MWD increased on average by approximately 20 meters with semaglutide[3] and approximately 15-20 meters with tirzepatide (in those able to perform 6MWT), compared to minimal changes on placebo. This objective gain in exercise capacity complements the self-reported symptom relief.
Weight loss and metabolic markers: GLP-1-based incretin agonist therapy led to profound weight loss (-10% to -12% of body weight on average) in these HFpEF populations[3,6]. This far surpassed lifestyle/placebo (approximately -2% to
HF events: While the semaglutide trials were not powered for hospitalization outcomes (and showed favorable trends), the larger and longer tirzepatide trial clearly demonstrated a reduction in HF events[6]. This provides proof-of-concept that treating the obese HFpEF phenotype with metabolic therapy can modify disease course, cutting HF hospitalization risk by roughly one-third. No other pharmacologic therapy to date (aside from SGLT2 inhibitors) has shown such an effect in HFpEF, and the magnitude observed with tirzepatide (HR 0.62) is notable[6]. It should be emphasized that in pooled analyses of semaglutide trials, hospitalizations were numerically lower and overall serious adverse events significantly lower in treated patients than controls[5], supporting a beneficial impact on HF decompensation.
GLP-1-based incretin agonists were generally well-tolerated in this population, with safety profiles similar to those seen in non-HF patients with obesity. The most common adverse effects were gastrointestinal (nausea, transient vomiting) related to the drugs’ mechanism; these were usually mild to moderate. There were fewer serious adverse events and HF hospitalizations on active therapy than on placebo in multiple trials[3,5] an encouraging safety signal in a fragile cardiac population.
One safety consideration is the higher rate of study drug discontinuation with tirzepatide (approximately 6% vs 1% placebo) due to GI side effects[6]. Semaglutide at 2.4 mg had lower drop-out rates in HFpEF (e.g. approximately 2%-3% discontinuation), perhaps reflecting careful dose up-titration in trials[3]. Importantly, there were no significant differences in arrhythmias, hypotension, or hypoglycemia events between GLP-1-based incretin agonist and placebo groups in these studies. In summary, aside from manageable GI symptoms, no major safety concerns emerged; on the contrary, patients receiving GLP-1-based incretin agonists had fewer HF-related adverse outcomes. This indicates that improving the HF syndrome (via weight loss and unloading) translated into overall health benefits that outweighed transient side effects.
The evidence synthesized above suggests that GLP-1-based incretin agonists, through their weight-centric and pleiotropic effects, offer a transformative new therapy for HFpEF in patients with obesity. Semaglutide and tirzepatide consistently improved exercise tolerance, HF symptoms, and quality of life to a degree not seen with conventional HFpEF therapies[3,6]. Moreover, tirzepatide’s outcomes trial demonstrates that this approach can significantly reduce the composite of CV death or worsening HF events-a key hard endpoint in HF management[6]. The benefits appear to be mediated by substantial weight loss leading to relief of cardiac loading conditions, reduction in inflammation, and regression of adipose tissue and hypertrophied myocardium[7,8]. This aligns with the concept of the “obesity cardiomyopathy” component of HFpEF, whereby weight reduction addresses a root cause of HFpEF pathophysiology (via decreased visceral fat, improved hemodynamics, and metabolic health).
The absence of heterogeneity for KCCQ-CSS confirms highly consistent symptomatic benefit across trials, whereas moderate heterogeneity in weight loss likely reflects differences in baseline diabetes status and pharmacologic potency between semaglutide and tirzepatide.
Until recently, management of HFpEF has been challenging, with limited therapies showing outcome benefits. Neurohormonal antagonists (ACEi/ARB, beta-blockers) have not clearly improved HFpEF outcomes. Only SGLT2 inhibitors have demonstrated a modest reduction in HF hospitalization (approximately 17% relative risk reduction) in HFpEF trials[2]. The magnitude of benefit seen with GLP-1-based incretin agonists on HF symptoms and function is substantially larger than that seen with SGLT2 inhibitors in HFpEF (which mainly improved diuretic efficiency and modestly improved KCCQ by approximately +1-2 points). Thus, GLP-1-based incretin agonist therapy addresses a major gap in HFpEF care-particularly for the obese phenotype, which is common and often unresponsive to traditional HF therapies[2]. It is also noteworthy that GLP-1-based incretin agonists confer multi-system benefits (glycemic control, weight loss, potential renal benefits), which could positively affect the multiple comorbidities that frequently accompany HFpEF (diabetes, hypertension, kidney disease).
Patients enrolled in these trials had a BMI typically ≥ 30 (mean approximately 37) and mostly NYHA class II-III symptoms, reflecting the target population who stands to benefit. Caution should be used in extrapolating results to non-obese HFpEF patients-the trials specifically addressed the obesity-associated HFpEF phenotype. Likewise, long-term effects beyond approximately 1-2 years remain to be seen (though diabetes CV outcome trials with GLP-1 RAs support their long-term CV safety and benefit). Cost and access to these medications may also be considerations in broad implementation. An important diagnostic limitation specific to this population deserves acknowledgment: Obesity suppresses circulating natriuretic peptide levels (BNP and NT-proBNP) through increased peptide clearance and altered secretion, which may result in lower-than-expected values even in patients with true elevated filling pressures. This natriuretic peptide suppression could lead to underdiagnosis of HFpEF in obese individuals and introduces the risk that some enrolled patients had obesity-related dyspnea rather than genuine HFpEF with hemodynamic derangement. Future trials in this phenotype should specify minimum NT-proBNP thresholds adjusted for BMI, or require invasive hemodynamic confirmation, to strengthen diagnostic rigor and reduce enrollment heterogeneity. Additionally, although all three included trials used double-blind designs, the pronounced gastrointestinal side effects and substantial visible weight loss associated with GLP-1-based therapy may have allowed participants to infer their treatment allocation-a phenomenon termed functional unblinding. This is particularly relevant for the KCCQ-CSS outcome, which relies entirely on patient self-report. Functional unblinding could introduce performance or detection bias that inflates the perceived magnitude of symptomatic benefit. The objective outcomes (body weight, 6MWD, HF events) are less susceptible to this bias and provide complementary support for the clinical efficacy of these agents.
The striking evidence from 2023-2024 has prompted experts to consider GLP-1-based incretin agonists as part of a comprehensive HFpEF management strategy in obese individuals. A 2025 ACC scientific statement on managing obesity in HF highlights semaglutide and tirzepatide as promising therapies for symptomatic HFpEF patients with BMI ≥ 30, given their proven benefits in recent trials[9]. Ongoing and future studies will further clarify their role-for example, whether lower EF ranges (mid-range EF or HFrEF with obesity) also derive benefit, and the impact on longer-term outcomes like mortality. Research is also warranted into combination approaches (e.g. GLP-1-based incretin agonists plus SGLT2 inhibitors) which could theoretically confer additive benefits in HFpEF.
This systematic review and meta-analysis demonstrate that GLP-1–based incretin agonists provide consistent and clinically meaningful improvements in health status, functional capacity, and body weight in patients with obesity-related HFpEF. Quantitative synthesis confirms robust gains in KCCQ-CSS with minimal heterogeneity and substantial weight reduction across trials, supporting a weight-centric disease-modifying approach in this HFpEF phenotype. Tirzepatide further reduced the composite of CV death or worsening HF events, providing proof of concept that targeting obesity can favorably alter HFpEF outcomes. Collectively, these findings position GLP-1-based incretin agonists as a core emerging therapy for obese HFpEF patients, with potential to transform management pending longer-term outcome data and integration into guideline-directed care.
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