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May 23, 2022CirculationOpen Access

Dapagliflozin increased ketone-related and short-chain acylcarnitine as well as medium-chain acylcarnitine metabolite clusters compared with placebo (nominal P=0.01, false discovery rate-adjusted P=0.08 for both clusters).

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Why the study?

SGLT2 inhibitors are foundational therapy in HFrEF, but the underlying mechanisms of benefit are not well defined.

Does dapagliflozin alter metabolic pathways compared to placebo in patients with HFrEF?

Population

234 HFrEF patients with targeted metabolomic data

Comparison

Dapagliflozin vs placebo

Design

Placebo-controlled trial

Follow-up

12 weeks

Authors

SSSenthil SelvarajZFZhuxuan FuPJPhilip G. Jones

Discussion

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Overview

Dapagliflozin-associated metabolomic shifts in HFrEF warrant mechanistic follow-up; leaves open whether ketone or acylcarnitine changes mediate outcomes.

Structured PICO

Does dapagliflozin alter metabolic pathways compared to placebo in patients with HFrEF?

P
Population
234 participants with heart failure with reduced ejection fraction (HFrEF), mean age 62.0±11.1 years, 25% women, 38% Black, mean ejection fraction 27±8%.
I
Intervention
Dapagliflozin
C
Comparator
Placebo
O
Outcome
Changes in principal components analysis-defined metabolite clusters (63 metabolites) at 12 weekssurrogate

Dapagliflozin alters key metabolic pathways in HFrEF, supporting a role for altered ketone and fatty acid biology as a potential mechanism of benefit.

Cite This Study

Selvaraj et al. (2022) studied this question.

synapsesocial.com/papers/6a7d17072935e92dbc775576https://doi.org/10.1161/circulationaha.122.060402
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Also Consider

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

  1. 1Targeted Metabolomic Profiling of Dapagliflozin in Heart Failure With Preserved Ejection Fraction2024 · 8 citations
  2. 2Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction2019 · 436 citations
  3. 3Impact of Dapagliflozin on Gut Microbiota and Plasma Metabolomic Profiles in Patients With Heart Failure2025 · 3 citations
  4. 4Metabolic remodeling and cardiac functional adaptation mediated by dapagliflozin in patients with acute heart failure: a retrospective cohort study2026
  5. 5The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial2021 · 622 citations