# Dual SGLT1/2 inhibition with sotagliflozin: a pharmaceutical breakthrough in heart failure management and cardiometabolic risk reduction

**Authors:** Ghaith K. Mansour, Sarah B. Hammo, Muhammad Raihan Sajid

PMC · DOI: 10.3389/fmed.2025.1733918 · Frontiers in Medicine · 2026-01-02

## TL;DR

Sotagliflozin, a new drug that blocks two types of glucose transporters, shows promise in treating heart failure and reducing cardiometabolic risks.

## Contribution

This paper reviews the novel dual SGLT1/2 inhibition mechanism of sotagliflozin and its clinical benefits in heart failure and cardiometabolic risk reduction.

## Key findings

- Sotagliflozin reduces cardiovascular events and heart failure hospitalizations in patients with and without diabetes.
- The drug improves glycemic control and has favorable effects on blood pressure and body weight.
- It shows a generally good safety profile but requires monitoring for specific side effects.

## Abstract

Heart failure remains a global health crisis with high morbidity and mortality. Sotagliflozin, a first-in-class dual sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor, offers a novel therapeutic approach. Its dual mechanism concurrently inhibits renal (SGLT2) and intestinal (SGLT1) glucose transporters, enhancing glycemic control and providing additive benefits in cardiovascular risk reduction, blood pressure, and body weight management. Recent randomized trials demonstrate that sotagliflozin significantly lowers the risk of major cardiovascular events, heart failure hospitalizations, and all-cause mortality in patients with and without diabetes. While its safety profile is generally favorable, it necessitates monitoring for gastrointestinal effects and diabetic ketoacidosis. This review synthesizes mechanistic insights, clinical evidence, and practical considerations for integrating sotagliflozin into heart failure management, positioning it as a promising innovation in cardiometabolic therapeutics.

## Linked entities

- **Proteins:** SLC5A1 (solute carrier family 5 member 1), SLC5A2 (solute carrier family 5 member 2)
- **Chemicals:** sotagliflozin (PubChem CID 24831714)
- **Diseases:** heart failure (MONDO:0005252), diabetic ketoacidosis (MONDO:0012819)

## Full-text entities

- **Genes:** SLC5A1 (solute carrier family 5 member 1) [NCBI Gene 6523] {aka D22S675, NAGT, SGLT-1, SGLT1}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}
- **Diseases:** Heart failure (MESH:D006333), diabetic ketoacidosis (MESH:D016883), diabetes (MESH:D003920)
- **Chemicals:** Sotagliflozin (MESH:C575681)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12808403/full.md

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Source: https://tomesphere.com/paper/PMC12808403