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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Indication assessment · §2

Heart failure with preserved ejection fraction and obesity — evidence across compounds

Every compound the Institute assesses in heart failure with preserved ejection fraction and obesity, with its certainty rating.

Document identifier
CEI-IN-06/2
Series
Indication assessment
Version
2.0
Published
29 Jan 2025
Last reviewed
29 Jan 2025
Next review
29 Jan 2027
Identifier
10.71829/cei.ind.6
Certainty
Not rated
Cycle
2025 Q1
ICD-11
BD10
Category
Cardiovascular

§2Evidence across compounds

Every compound the Institute assesses in this indication, with the effect as recorded, the certainty rating and the contributing trials. Effects are reported on the anchor outcome where the contributing trials measured it and on the outcome the trial actually reported where they did not.

Table 1. Compounds assessed in heart failure with preserved ejection fraction and obesity, ordered by certainty.

CompoundEffect as recordedInterval as reportedCertaintyTrials
SemaglutideGLP-1 receptor agonist (acylated, long-acting)KCCQ clinical summary score improvement of 7.8 points versus placebo at 52 weeksestimated difference 7.8 points (95 % CI 4.8 to 10.9)Moderate2
TirzepatideDual GIP and GLP-1 receptor agonist (acylated)Composite of cardiovascular death or worsening heart failure hazard ratio 0.62HR 0.62 (95 % CI 0.41 to 0.95); KCCQ difference 6.9 points (95 % CI 3.3 to 10.6)Moderate1
SS-31 (elamipretide)Mitochondria-targeted cardiolipin-binding tetrapeptideA phase 2 trial in heart failure with preserved ejection fraction did not demonstrate benefit on the primary endpointnegative resultLow1
Estimates in this table are not on a common scale and must not be subtracted from one another. Where a comparison between two compounds has been made directly, it appears in a synthesis and not here.
Compounds assessed in HFpEFPoint estimates with confidence intervals for each contributing study, plotted against the line of no effect.0.00.20.40.60.8Standardised direction and relative magnitudeCompoundEffect as recordedSemaglutideModerate certaintyKCCQ clinical summary score…TirzepatideModerate certaintyComposite of cardiovascular death…SS-31 (elamipretide)Low certaintyA phase 2 trial in heart failure…
Moderate or high certaintyLow or very low certainty
Figure 1. Illustrative. Compounds assessed in this indication, plotted on a common standardised axis so that direction and relative magnitude can be compared at a glance. The estimates are not on a common natural scale and the intervals are the Institute's standardised representation of the reported precision rather than published confidence intervals.

§2.1Syntheses bearing on this indication

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine 2021;384(11):989–1002. doi:10.1056/NEJMoa2032183 · PMID 33567185
  2. Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet 2021;397(10278):971–984. doi:10.1016/S0140-6736(21)00213-0 · PMID 33667417

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

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