Secondary Analysis Shows INPEFA® Benefits Heart Failure Patients Regardless of Diabetes Duration

Lexicon Pharmaceuticals, Inc. announced that new analysis from the Phase 3 SCORED clinical trial revealed that INPEFA® (sotagliflozin) significantly reduced the risk of major adverse cardiovascular events (MACE) and heart failure (HF) across different durations of diabetes. The findings, presented at the European Society of Cardiology (ESC) Congress 2024 in London, demonstrated that patients with longer durations of diabetes benefitted even more from the treatment, while all patients showed improvement regardless of how long they had diabetes.

Cardiovascular disease (CV) is a major risk factor for people with diabetes, especially those with a longer history of the condition. The study aimed to determine if the duration of diabetes influenced the effectiveness of INPEFA. The primary endpoint was a composite measure of cardiovascular death, heart failure hospitalization, and urgent heart failure visits. Secondary endpoints included MACE components like cardiovascular death, nonfatal heart attack, and nonfatal stroke.

The study involved 10,579 patients with varying durations of diabetes: 2,412 patients with less than 10 years, 4,424 patients with 10-19 years, and 3,743 patients with 20 or more years of diabetes. The median duration was 16.4 years, and mean hemoglobin A1c levels were similar across groups. Results showed that the rate of the primary endpoint was significantly lower in the INPEFA group (5.6 events per 100 patient-years) compared to the placebo group (7.5 events per 100 patient-years).

Event rates by diabetes duration indicated that INPEFA's benefit increased with longer diabetes duration: 5.6 vs. 5.8 events per 100 patient-years for less than 10 years, 6.1 vs. 7.4 events per 100 patient-years for 10-19 years, and 4.6 vs. 8.5 events per 100 patient-years for 20 or more years. Further analysis showed increasing treatment benefit with increasing diabetes duration.

Similar trends were observed for secondary heart failure outcomes, such as hospitalization for heart failure or urgent visits for heart failure, which also showed increased benefit with longer diabetes duration. Overall, MACE was lower in the INPEFA group (4.8 events per 100 patient-years) compared to the placebo group (6.3 events per 100 patient-years).

Dr. Craig Granowitz, Lexicon’s senior vice president and chief medical officer, emphasized that the analysis reinforces previous clinical data, demonstrating significant risk reductions in heart failure and MACE events in heart failure patients treated with INPEFA. He stressed the importance of these findings for patients, clinicians, and payers, highlighting INPEFA’s unique position among SGLT2 inhibitors.

INPEFA is an oral inhibitor targeting two proteins responsible for glucose regulation, known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). It has been evaluated in various patient populations, including those with heart failure, diabetes, and chronic kidney disease, across clinical studies involving approximately 20,000 patients.

INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.

Patients considering INPEFA should have their renal function and volume status assessed before starting treatment. It is contraindicated in individuals with hypersensitivity to its components and those with a risk of ketoacidosis, among other conditions. Common adverse reactions include urinary tract infections, volume depletion, diarrhea, and hypoglycemia. Specific populations, such as pregnant women, the elderly, and those with renal or hepatic impairment, should also consider specific precautions.