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Purpose of Review <p>The global obesity epidemic has precipitated a surge in obesity-related heart failure with preserved ejection fraction (HFpEF), a distinct clinical phenotype characterized by exacerbated symptom burden, systemic inflammation, and impaired quality of life compared to non-obese HFpEF. While lifestyle modifications remain foundational, suboptimal adherence limits their efficacy. Bariatric surgery leads to the most dramatic and sustained weight loss but lacks a randomized trial for HFpEF-specific outcomes.</p> Recent Findings <p>Recent landmark trials (STEP-HFpEF, STEP-HFpEF DM, SUMMIT) demonstrate that incretin-based therapies—glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists—significantly ameliorate heart failure symptoms, attenuate heart failure worsening, and induce weight loss in obese HFpEF patients, irrespective of diabetes status. However, long-term cardiovascular mortality benefits and safety profiles require further validation. Sodium-glucose cotransporter-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists MRAs exhibit prognostic benefits in HFpEF, with post hoc analyses suggesting enhanced efficacy in higher BMI subgroups. Conversely, angiotensin receptor-neprilysin inhibitors and the controlled metabolic accelerator HU6 lack randomized trials to support routine use.</p> Summary <p>A combination of incretin-based therapies, SGLT2 inhibitors, and non-steroidal MRAs may represent the optimal evidence-based strategy for obesity-related HFpEF at present. Future research should prioritize standardized definitions of obesity, BMI thresholds, weight loss targets, optimal combination strategies, and long-term outcome assessments.</p>

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Advances in Pharmacotherapies for Obesity-Related HFpEF: A Comprehensive Review

  • 期刊论文

  • 发表日期：

    2025年10月29日

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  • Ying Wu,
  • Meiyan Song,
  • Xiaomin Chen,
  • Wen Chen,
  • Meifang Wu,
  • Liming Lin

摘要

Purpose of Review

The global obesity epidemic has precipitated a surge in obesity-related heart failure with preserved ejection fraction (HFpEF), a distinct clinical phenotype characterized by exacerbated symptom burden, systemic inflammation, and impaired quality of life compared to non-obese HFpEF. While lifestyle modifications remain foundational, suboptimal adherence limits their efficacy. Bariatric surgery leads to the most dramatic and sustained weight loss but lacks a randomized trial for HFpEF-specific outcomes.

Recent Findings

Recent landmark trials (STEP-HFpEF, STEP-HFpEF DM, SUMMIT) demonstrate that incretin-based therapies—glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists—significantly ameliorate heart failure symptoms, attenuate heart failure worsening, and induce weight loss in obese HFpEF patients, irrespective of diabetes status. However, long-term cardiovascular mortality benefits and safety profiles require further validation. Sodium-glucose cotransporter-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists MRAs exhibit prognostic benefits in HFpEF, with post hoc analyses suggesting enhanced efficacy in higher BMI subgroups. Conversely, angiotensin receptor-neprilysin inhibitors and the controlled metabolic accelerator HU6 lack randomized trials to support routine use.

Summary

A combination of incretin-based therapies, SGLT2 inhibitors, and non-steroidal MRAs may represent the optimal evidence-based strategy for obesity-related HFpEF at present. Future research should prioritize standardized definitions of obesity, BMI thresholds, weight loss targets, optimal combination strategies, and long-term outcome assessments.