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September 21, 2026Heart Failure ReviewsOpen Access

SGLT2i, GLP-1/GIP RAs, and MRAs improve cardiorenal outcomes in HFpEF by targeting interconnected organ systems.

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Why the study?

HFpEF is a systemic disease with complex interactions among cardiac and extracardiac mechanisms, and therapeutic options have historically been limited despite high prevalence and poor prognosis.

Population

Patients with HFpEF and metabolic comorbidities including obesity, type 2 diabetes, and chronic kidney disease

Comparison

Effects of novel therapies including SGLT2 inhibitors, GLP-1 receptor agonists, dual incretin therapies, and mineralocorticoid receptor antagonists

Design

Narrative review synthesizing pathophysiology and therapeutic effects

Key result

Novel therapies including SGLT2 inhibitors, GLP-1/GIP receptor agonists, and mineralocorticoid receptor antagonists improve cardiovascular and renal outcomes in patients with HFpEF by targeting interconnected organ systems.

Authors

SNSoufiane NassiriMHM. Louis HandokoABArno A. van de Bovenkamp

Discussion

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Overview

Supports cardiometabolic therapies in HFpEF via multiorgan effects; extends mechanistic synthesis but leaves open prospective RCT confirmation.

Structured PICO

P
Population
Patients with heart failure with preserved ejection fraction (HFpEF) and metabolic comorbidities (obesity, type 2 diabetes, and chronic kidney disease)
I
Intervention
Sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 (GLP-1) receptor agonists, dual incretin therapies (GLP-1/GIP RAs), and (non-steroidal) mineralocorticoid receptor antagonists

This review synthesizes the pathophysiological interactions in HFpEF and maps the clinical and mechanistic effects of novel therapies across interconnected organ systems.

Limitations

  • Much of the available human evidence for microvascular dysfunction is cross-sectional or associative, making causal attribution difficult.
  • Smaller sample sizes of HFpEF-specific studies for GLP-1 receptor agonists may limit generalizability.

Cite This Study

Nassiri et al. (2026) conducted a review in Heart failure with preserved ejection fraction (HFpEF). SGLT2 inhibitors, GLP-1/GIP receptor agonists, and mineralocorticoid receptor antagonists was evaluated. Novel therapies including SGLT2 inhibitors, GLP-1/GIP receptor agonists, and mineralocorticoid receptor antagonists improve cardiovascular and renal outcomes in patients with HFpEF by targeting interconnected organ systems.

synapsesocial.com/papers/6ab46f9e77b2723afff94a8ahttps://doi.org/10.1007/s10741-026-10671-x
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Heart Failure With Preserved Ejection Fraction With CKD: A Narrative Review of a Multispecialty Disorder2023 · 44 citations
  2. 2Advances in extracardiac mechanisms for heart failure with preserved ejection fraction.2022 · 2 citations
  3. 3Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease2024 · 11 citations
  4. 4Chronic Kidney Disease as a Risk Factor for Heart Failure With Preserved Ejection Fraction: A Focus on Microcirculatory Factors and Therapeutic Targets2019 · 88 citations
  5. 5Focusing on microvascular function in heart failure with preserved ejection fraction2025 · 10 citations