Published in the Journal of Clinical Investigation, researchers at University of Michigan Medical School looked for the mechanism behind sotagliflozin’s cardiovascular benefits. Sotagliflozin is FDA-approved as Inpefa for adults with heart failure, and for those with type 2 diabetes, chronic kidney disease and other cardiovascular risk factors.
Key findings:
- The problem: For people with type 2 diabetes, dangerous blood clots from overactive platelets are a major cause of heart attack and stroke.
- What makes sotagliflozin different: It is a dual inhibitor — it blocks both SGLT2 in the kidneys and SGLT1 in other organs. Most common drugs in this class, like empagliflozin (Jardiance) and dapagliflozin (Farxiga), only block SGLT2.
- Head-to-head lab tests: In blood samples from both healthy volunteers and people with type 2 diabetes, sotagliflozin limited excessive platelet activation. Empagliflozin had little to no effect.
- Anti-clotting effect: Sotagliflozin made platelets less likely to stick together. In mice with injured blood vessels, it reduced clot formation by about 60%, compared to 5-10% for empagliflozin.
- Why it works: Blocking SGLT1 in platelets alone reduced clotting by about 40% in mice, but didn’t fully explain sotagliflozin’s effect. A selective SGLT1 blocker, mizagliflozin, also didn’t replicate the full effect. Researchers think additional mechanisms — possibly involving SGLT1 in endothelial cells that line blood vessels — are involved.
What the researchers said:
Co-senior authors Dr. Michael Holinstat and Dr. Eugene Chen noted that blocking SGLT2 alone is not enough to inhibit platelet aggregation, and that sotagliflozin may offer protection against clots without increasing bleeding risk — a long-sought goal in clot prevention.
Co-author Dr. Bertram Pitt said sotagliflozin appears to be in a “sweet spot” because highly selective SGLT1 inhibitors can cause gastrointestinal issues.
Next steps and limitations:
The work was laboratory and animal research, not a clinical trial in patients. The authors say future studies should look at effects in conditions like chronic kidney disease and atrial fibrillation.
This is early mechanistic research. If you have questions about diabetes treatment and cardiovascular risk, it’s best to discuss them with your doctor or healthcare team.