Sotagliflozin, a drug approved by the Food and Drug Administration to treat type 2 diabetes and kidney disease with additional cardiovascular risk factors, can significantly reduce heart attack and stroke among these patients, according to results from an international clinical trial led by Deepak L. Bhatt, MD, MPH, MBA, Director of Mount Sinai Fuster Heart Hospital.
Sotagliflozin—a sodium-glucose cotransporter (SGLT) inhibitor—blocks the function of two proteins, SGLT1 and SGLT2, which move glucose and sodium across cell membranes and help control blood sugar levels. Other SGLT2 inhibitors do not as significantly block SGLT1.
The study, published in February 2025 in The Lancet Diabetes & Endocrinology, is the first to show that an SGLT inhibitor has these unique cardiovascular benefits.
“These results demonstrate a new mechanism of action—combined blockade with sotagliflozin of the SGLT1 receptors (found in the kidney, gut, heart, and brain) and SGLT2 receptors (found in the kidney)—to reduce heart attack and stroke risk,” says Dr. Bhatt, chair of the study, and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai. “The benefits seen here are distinct from those seen with the other very popular SGLT2 inhibitors in widespread clinical use for diabetes, heart failure, and kidney disease.”
The study was a prespecified secondary analysis of the SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) trial. It was funded by Lexicon Pharmaceuticals.
The time to clinical benefit was assessed: The x axis represents time from randomization, and the y axis represents the degree of benefit at that time, as measured by the hazard ratio shown in blue. The vertical black line marks the day that the treatment benefit of sotagliflozin reached and maintained statistical significance. Despite the SCORED trial enrolling stable patients, by just three months, there was already a significant decrease in heart attacks and strokes, a very early benefit that is generally not seen with medications used in non-acute settings.
The double-blind, placebo-controlled, randomized clinical trial analyzed the ability of sotagliflozin to reduce the risks of life-threatening cardiovascular outcomes. Researchers enrolled 10,584 patients with chronic kidney disease, type 2 diabetes, and additional cardiovascular risk factors; randomly assigned them to sotagliflozin or placebo; and followed them for an average of 16 months. Sotagliflozin treatment was prescribed at 200 mg once a day, with the dose increased to 400 mg once a day within the first six months if tolerated. A matching placebo was prescribed at the same treatment frequency as the intervention regimen. A prespecified secondary outcome was total major adverse cardiovascular events (MACE), a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Other outcomes included total myocardial infarction and total stroke (fatal and nonfatal events).
The study found that patients in the sotagliflozin group had a significantly lower rate of total MACE than those in the placebo group (4.8 events per 100 person-years vs. 6.3 events per 100 person-years.) Additionally, sotagliflozin significantly reduced the rate of myocardial infarction (1.8 events per 100 person-years vs. 2.7 events per 100 person-years), and stroke (1.2 events per 100 person-years vs. 1.8 events per 100 person-years) compared with placebo.
Overall, the patients in the sotagliflozin group had a 23 percent reduction in the rate of heart attacks, strokes, and deaths from such cardiovascular causes compared with the placebo group.
“Physicians now have a new option to reduce global cardiovascular risk such as heart failure, progression of kidney disease, heart attack, and stroke,” Dr. Bhatt says. “This drug was approved to reduce the risk of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent heart failure visits for patients with either heart failure or type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors. These important, new data show that it additionally reduces the risk of heart attacks and strokes, and we could see more widespread use as a result.”
The Icahn School of Medicine at Mount Sinai receives research funding from Lexicon Pharmaceuticals for Dr. Bhatt’s role as chair of the SCORED trial.
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Deepak L. Bhatt, MD, MPH, MBA
Director of the Mount Sinai Fuster Heart Hospital, and the Dr. Valentin Fuster Professor of Cardiovascular Medicine