INPEFA® (Sotagliflozin) Lowers Heart Failure Risk in Preserved Ejection Fraction: New Analysis

Lexicon Pharmaceuticals, Inc. has revealed a new post-hoc analysis of clinical data demonstrating that INPEFA® (sotagliflozin), a dual oral inhibitor of SGLT2 and SGLT1, significantly reduces the risk of heart failure-related events across a diverse patient population, including those with preserved ejection fraction (HFpEF). This study, presented at the Annual Congress of the Heart Failure Association of the European Society of Cardiology (ESC) in Lisbon, Portugal, indicates that INPEFA is particularly effective in patients with HFpEF related to obesity.

The growing prevalence of HFpEF is largely driven by obesity, type 2 diabetes (T2D), and an aging population. Recent studies in the journals of the American College of Cardiology and the American Heart Association highlight that individuals with obesity-related HFpEF represent a distinct and clinically significant subgroup. This analysis evaluated the influence of obesity, sex, and age on the effects of INPEFA in patients with left ventricular ejection fraction (LVEF) ≥ 50%. Previous data from the SOLOIST-WHF and SCORED trials had already established that INPEFA is effective in reducing cardiovascular (CV) death and heart failure (HF) outcomes across varying LVEF ranges.

The analysis included data from 1,932 patients with an average age of 69.9 years, a mean BMI of 34.1 kg/m², and a mean HbA1c of 8.5%. Among these patients, 18.1% experienced a primary endpoint event. Both male and female patients showed similar event rates of 18.3% and 18.0%, respectively. However, older patients (≥ 65 years) and those with higher BMI (≥ 30 kg/m²) were at increased risk for primary endpoint events.

In patients with a BMI of 30 kg/m² or higher, INPEFA therapy was notably effective, with a significant p-value for interaction (0.038). The response to INPEFA was consistent across sex and age subgroups, with p-values for interaction of 0.818 and 0.393, respectively.

Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer, stated, “This analysis underscores the importance of identifying patient risk factors such as age, sex, and obesity in patients with HFpEF and adds to the body of evidence differentiating INPEFA as a dual inhibitor of SGLT1 and SGLT2. Additionally, today’s data presentation further highlights the benefits of INPEFA in reducing the risk of heart failure-related events across a wide range of patients with HFpEF, including those with an obesity-related HFpEF phenotype.”

INPEFA® (sotagliflozin), discovered through Lexicon’s unique gene science approach, is an oral inhibitor of sodium-glucose cotransporters 2 and 1 (SGLT2 and SGLT1), which are critical for glucose regulation. SGLT2 aids in glucose and sodium reabsorption in the kidneys, while SGLT1 is involved in glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in clinical trials involving approximately 20,000 patients across various conditions, including heart failure, diabetes, and chronic kidney disease.

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 T2D, chronic kidney disease, and other cardiovascular risk factors.

The safety information highlights the need to assess renal function and volume status before initiating INPEFA and notes the contraindications and risks associated with its use, such as ketoacidosis, volume depletion, urinary tract infections, hypoglycemia, necrotizing fasciitis of the perineum, and genital mycotic infections. Drug interactions and use in specific populations, including pregnant and lactating women, geriatric patients, and those with renal or hepatic impairment, are also detailed to ensure informed and safe usage of the medication.