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Updated: Jan 9, 2026
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Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
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Targeting Metabolic Dysfunction and Inflammation with Sotagliflozin Reverses Diastolic Dysfunction in Experimental
Biorxiv : the Preprint Server for Biology
|December 11, 2025
Summary
Dual SGLT1/2 inhibition with sotagliflozin improved heart failure with preserved ejection fraction (HFpEF) in mice. It enhanced fatty acid oxidation and reduced inflammation, offering mechanistic insights into cardiometabolic benefits.
Area of Science:
- Cardiology
- Metabolic disease
- Pharmacology
Background:
- Heart failure with preserved ejection fraction (HFpEF) is common and linked to obesity, hypertension, and metabolic issues.
- SGLT2 inhibitors benefit HFpEF, but dual SGLT1/2 inhibition mechanisms are unclear.
Purpose of the Study:
- Investigate the mechanisms of dual SGLT1/2 inhibition by sotagliflozin in a murine model of cardiometabolic HFpEF.
- Elucidate how sotagliflozin impacts cardiac metabolism and inflammation.
Main Methods:
- A high-fat diet and L-NAME induced HFpEF in mice, treated with sotagliflozin or vehicle.
- Evaluated cardiac function, metabolism, gene expression, and immune cell profiles.
Main Results:
- Sotagliflozin reduced weight gain, improved glucose tolerance, and enhanced cardiac fatty acid oxidation.
- It normalized diastolic dysfunction, reduced cardiac fibrosis, and suppressed inflammatory pathways and immune cell infiltration.
- Systemic inflammation markers were also attenuated.
Conclusions:
- Dual SGLT1/2 inhibition with sotagliflozin offers cardiometabolic benefits in experimental HFpEF.
- It reprograms metabolism towards lipid utilization and reduces inflammation, targeting the metabolic-inflammatory axis in HFpEF.
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