Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure.

Objective: To describe the pharmacology, clinical efficacy, and safety evidence of sotagliflozin, the first approved dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in heart failure (HF) management.

Data sources: A literature search of studies published between January 2012 and September 2023 were identified using PubMed, MEDLINE, and clinicaltrials.gov with search terms of "sotagliflozin," "Inpefa," or "LX4211."

Study selection and data extraction: All available studies in English were considered. Studies were included if they investigated drug pharmacology, efficacy, or safety information.

Data synthesis: Two phase 3 trials of sotagliflozin, SOLOIST-WHF and SCORED, evaluated sotagliflozin compared with placebo in patients with type 2 diabetes mellitus (T2DM). SOLOIST-WHF reported a statistically decreased rate of cardiovascular and HF events with sotagliflozin (hazard ratio [HR] = 0.67, 95% CI = 0.52-0.85), while SCORED found a statistically significant decrease in incidence of cardiovascular events in patients with T2DM, chronic kidney disease (CKD), and risk factors for cardiovascular disease in patients in the sotagliflozin group (HR = 0.74, 95% CI = 0.63-0.88).

Relevance to patient care and clinical practice in comparison to existing agents: While approval of sotagliflozin expands treatment options for patients with HF, the SGLT2 inhibitors, dapagliflozin and empagliflozin, have more data supporting their use in HF, additional risk reduction benefits in patients with CKD, and approval for use in T2DM. Landmark trials of sotagliflozin required a previous diagnosis of T2DM, despite the broader approved indication. Where sotagliflozin will be adopted into the treatment of HF is unclear due to the evidence and benefits of already established SGLT2 inhibitors and the need for comparison with SGLT2 inhibitors.

Conclusion: Given the limitations of currently available evidence, including difficulty in fully interpreting the trial results due to changes in primary endpoints, not adjudicating the events, and not reaching the original power calculations, more investigation is warranted to determine the benefit of sotagliflozin compared with SGLT2 inhibitors.