A Review of Sotagliflozin: The First Dual SGLT-1/2 Inhibitor

Sotagliflozin (trade name INFEPA) is a novel dual sodium-glucose cotransporter-1 and -2 (SGLT-1/2) inhibitor that was developed by Lexicon Pharmaceuticals. It has emerged as a promising therapy for managing heart failure and other cardiovascular complications associated with type 2 diabetes mellitus (T2DM). Its dual inhibition of SGLT-1 and SGLT-2 receptors uniquely decreases glucose absorption in the intestine in addition to decreasing renal glucose reabsorption, leading to improved glycemic control and cardio-reno protection. Clinical trials have demonstrated its efficacy in reducing cardiovascular death, heart failure hospitalizations, and urgent visits, particularly in T2DM patients with chronic kidney disease (CKD). The drug was approved in 2023 by the Food and Drug Administration for reducing cardiovascular death and heart failure in T2DM patients with CKD and those with heart failure, irrespective of diabetic status or ejection fraction. However, despite its considerable therapeutic potential, sotagliflozin does pose notable adverse effects, including diabetic ketoacidosis, genital infections, and diarrhea. As a result, it has faced regulatory challenges in certain regions, notably the United States. The Food and Drug Administration has so far withheld approval for sotagliflozin in the treatment of type 1 diabetes due to concerns about its safety profile, specifically the risk of diabetic ketoacidosis, although Lexicon Pharmaceuticals plans to submit another new drug application for this use in 2024. Further investigation and clinical trials are warranted to fully elucidate sotagliflozin’s impact on diabetes and CKD.