SynthesisFrontiers in cardiovascular medicine2026
GLP-1-Based therapies for obesity-related heart failure with preserved ejection fraction: an umbrella review incorporating broader heart failure and cardiometabolic evidence.
Synthesis in Frontiers in cardiovascular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
4 authors.
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Abstract
Background: The cardiometabolic phenotype of obesity-related heart failure with preserved ejection fraction (HFpEF) is increasing in clinical prevalence. Existing systematic reviews and meta-analyses have primarily summarized efficacy estimates for glucagon-like peptide-1 (GLP-1)-based therapies, but the credibility and independence of these syntheses remain uncertain because methodological limitations and overlap in primary trials have not been systematically evaluated. This umbrella review therefore appraised the methodological quality, overlap, consistency, and robustness of the existing review-level evidence rather than generating another efficacy synthesis. Methods: We conducted an umbrella review of systematic reviews, meta-analyses, and network meta-analyses evaluating GLP-1-based regimens in obesity-related HFpEF and adjacent cardiometabolic populations. PubMed, Embase, Web of Science, and the Cochrane Library were searched over the preceding decade. The systematic review or meta-analysis was the unit of analysis. Methodological quality was assessed with AMSTAR 2, and overlap of primary studies across reviews was quantified using the corrected covered area (CCA). No Results: Seventeen systematic reviews underwent qualitative profiling, of which 11 reported quantitative estimates relevant to the core review-level synthesis. For heart failure hospitalization, the review by Diallo et al. reported HR 0.78 (95% CI 0.73-0.84; Conclusions: At the level of existing evidence syntheses, GLP-1-based therapies appear most consistently associated with fewer heart failure hospitalizations and improved functional capacity in obesity-related HFpEF. However, the review-level evidence does not establish a consistent mortality benefit or support GLP-1-based therapy as a universal mortality-modifying treatment for HFpEF. These agents are better interpreted as emerging metabolic-functional therapies whose apparent benefits must be considered in light of methodological limitations and high overlap among reviews.
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