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Sotagliflozin: Two Birds with One Stone?
Juan Antonio Requena-Ibáñez1, Kristine Mørk Kindberg2,3, Carlos G Santos-Gallego4
1Atherothrombosis Research Unit, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., New York, NY, 10029-0310, USA. juanantonio.requenaibanez@mssm.edu.
Cardiovascular Drugs and Therapy
|June 4, 2025
Summary
Dual SGLT1-2 inhibitors, like sotagliflozin, show promise in reducing major adverse cardiovascular events, including heart attack and stroke, potentially offering greater benefits than SGLT2 inhibitors alone for heart failure patients.
Area of Science:
- Cardiology
- Pharmacology
- Metabolic Diseases
Background:
- Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are established treatments for heart failure (HF), reducing major adverse cardiovascular events (MACE).
- SGLT2i do not significantly impact atherothrombotic events like myocardial infarction (MI) or stroke.
- Sotagliflozin is a novel dual inhibitor of SGLT1 and SGLT2.
Purpose of the Study:
- To compare the cardiovascular benefits of dual SGLT1-2 inhibition versus SGLT2 inhibition alone.
- To explore the role of SGLT1 in cardiovascular pathophysiology and its potential as a therapeutic target.
- To evaluate the impact of sotagliflozin on MACE, MI, and stroke.
Main Methods:
- A comprehensive literature review of studies published within the last five years was performed.
- Databases searched included PubMed and Scopus.
- Article selection was based on relevance, methodological quality, and citation impact.
Main Results:
- SGLT1 and SGLT2 share roles in glucose reabsorption, with SGLT1 also involved in intestinal glucose absorption.
- SGLT1 is overexpressed in failing hearts, contributing to oxidative stress, cardiomyocyte hypertrophy, and fibrosis.
- SGLT1 inhibition by sotagliflozin may reverse detrimental metabolic changes in the heart and reduce platelet activation.
- Sotagliflozin demonstrated reductions in MACE, MI, and stroke, unlike SGLT2i alone.
Conclusions:
- Dual SGLT1-2 inhibition may provide additional cardiovascular benefits beyond SGLT2 inhibition.
- Further research is needed to elucidate the distinct clinical impacts of SGLT2i versus SGLT1-2i.
- Comparative and mechanistic studies are essential, especially in non-diabetic patients with heart failure.
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