Network Meta-Analysis Ranks Treatments for Heart Failure with Preserved Ejection Fraction | Research

The takeaway

An updated network meta-analysis compares emerging and established therapies for HFpEF — including GLP-1 agonists and SGLT2 inhibitors — highlighting adiposity-targeting approaches as central to treatment.

Adiposity-targeting approaches central
Network meta-analysis reframes HFpEF treatment around metabolic and weight interventions

What the researchers found

Network meta-analysis comparing HFpEF therapies suggests adiposity-targeting approaches are central to treatment, with emerging metabolic therapies showing comparative effectiveness.

Why it matters

HFpEF affects half of all heart failure patients but has had no definitive treatment until recently. This analysis helps rank the growing number of options for the first time.

How the study worked

Systematic review and network meta-analysis of RCTs from PubMed, Embase, and Cochrane Library through April 2025.

What this study cannot tell us

HFpEF is heterogeneous; network meta-analysis assumptions may not hold across all phenotypes; limited long-term outcome data for newer therapies.

How to read the evidence

Network meta-analysis of RCTs — highest evidence synthesis level for comparative effectiveness.

When this study was published

Published in 2026 with evidence through April 2025, providing the most current HFpEF treatment comparison.

The bigger picture

Reframing HFpEF as partly a metabolic disease of adiposity fundamentally changes treatment strategy — from hemodynamic interventions to metabolic approaches including GLP-1 drugs and weight management.

Questions still open

Should GLP-1 drugs be first-line for obese HFpEF patients?
Can HFpEF phenotyping help match patients to the most effective therapy?

Common questions

What is HFpEF and why is it hard to treat?

HFpEF is heart failure where the heart pumps normally but doesn't fill properly. It affects half of all heart failure patients but has had few effective treatments until recently — partly because we didn't fully understand its causes.

Why does targeting obesity help HFpEF?

Growing evidence shows excess body fat contributes directly to HFpEF through inflammation, metabolic stress, and increased blood volume. Treatments that reduce adiposity may address a root cause rather than just symptoms.

Read the original research

Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta-analysis.

Diabetes, obesity & metabolism

View on PubMed ↗Publisher’s paper ↗

Citation

Chen, Szu-Han; Tseng, Yu-Wen; Huang, Chi-Jung; Yang, Shu-Mei; Fudim, Marat; Chuang, Shao-Yuan; Sung, Shih-Hsien; Cheng, Hao-Min. (2026). Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta-analysis.. Diabetes, obesity & metabolism. https://doi.org/10.1111/dom.70503