Sotagliflozin Lowers A1c, Weight Even in Kidney Impairment

Sotagliflozin (Inpefa) is a novel oral medication that inhibits both sodium-glucose cotransporter 1 (SGLT1) and sodium-glucose cotransporter 2 (SGLT2). This dual mechanism allows it to reduce glucose absorption in the intestines and increase glucose excretion through the kidneys. While it is not approved for lowering blood sugar in type 2 diabetes, recent studies have shown that it can reduce hemoglobin A1c (HbA1c) levels and body weight, even in patients with chronic kidney disease (CKD).Verywell Health

Clinical Findings

A meta-analysis presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2025 evaluated the effects of sotagliflozin on HbA1c and body weight in patients with type 2 diabetes across different levels of kidney function. The analysis included data from eight double-blind, randomized, placebo-controlled trials with over 4,000 participants.

Participants were divided into three subgroups based on their estimated glomerular filtration rate (eGFR):

- Subgroup 1: eGFR ≥ 60 mL/min/1.73m² (normal kidney function)

- Subgroup 2: eGFR 30 to <60 mL/min/1.73m² (moderate CKD)

- Subgroup 3: eGFR <30 mL/min/1.73m² (severe CKD)

Patients received either 200 mg or 400 mg of sotagliflozin daily or a placebo. The results showed that both doses significantly reduced HbA1c and body weight compared to placebo in the overall population and in Subgroup 1. In Subgroup 2, the 400 mg dose significantly reduced HbA1c, while both doses reduced body weight. In Subgroup 3, the 400 mg dose led to significant weight loss, but the reduction in HbA1c was not statistically significant.

FDA Approval and Indications

In May 2023, the U.S. Food and Drug Administration (FDA) approved sotagliflozin for reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure, type 2 diabetes, CKD, and other cardiovascular risk factors. However, it is not approved specifically for lowering blood sugar in type 2 diabetes. Previous applications for its use in type 1 diabetes were declined due to concerns about diabetic ketoacidosis.

Expert Opinions

Dr. Sara E. Lubitz, an associate professor of medicine at Rutgers Robert Wood Johnson Medical School, commented on the findings, stating that sotagliflozin could be as effective as other SGLT2 inhibitors for patients with heart failure and diabetes, offering both cardiovascular protection and blood sugar reduction. However, she noted that it is not currently considered a first-line treatment.

Conclusion

Sotagliflozin offers multiple benefits for patients with type 2 diabetes and CKD, including reductions in HbA1c, body weight, and cardiovascular events. Its dual inhibition of SGLT1 and SGLT2 provides a unique mechanism of action that may be particularly beneficial for patients with varying degrees of kidney function. While not approved for glycemic control in type 2 diabetes, it remains a valuable option for reducing cardiovascular risks in this population.

Source

Sotagliflozin Lowers A1c, Weight Even in Kidney Impairment