New Data Shows Positive Results for Sotagliflozin for Patients With Chronic Kidney Disease, Diabetes

Two abstracts will be presented on sotagliflozin (Inpefa; Lexicon Pharmaceuticals) at the American College of Cardiology Conference from April 6 to April 8, 2024, in Atlanta, Georgia. In abstract 1, investigators aimed to determine the effects of sotagliflozin on platelet activation as a possible explanation on the effects on myocardial infarction (MI) and stroke, and abstract 2 focuses on the efficacy of sotagliflozin on all-cause and cause-specific stroke outcomes for those with diabetes, chronic kidney disease (CKD), and high cardiovascular disease (CVD) risk.^1,2

Sotagliflozin is a sodium-glucose cotransporter 1 (SGLT) inhibitor and SGLT1 inhibitor, and has been the first to demonstrate reductions in both MI and stroke in individuals with type 2 diabetes (T2D) and CKD. Investigators evaluated the efficacy of sotagliflozin in modulating human platelet activation. Patients were treated with sotagliflozin and were stimulated with adenine di-phosphate (ADP). They were also assessed for aggregation and dense granule secretion as well as integrin αIIbβ3 activation and alpha granule secretion, according to the authors of the abstract.¹

Sotagliflozin demonstrated the ability to inhibit ADP-induced platelet aggregation starting at 10 μM of sotagliflozin, according to the abstract authors. Further, it inhibited more than 50% integrin activation and alpha granule secretion, which was assessed by investigators through expression of P-selectin. For dense granule secretion, investigators found that it was shown to be dose-dependently sensitive to sotagliflozin.¹

Investigators concluded that these results could potentially show the mechanisms for how sotagliflozin reduces stroke and MI as well as provide insight into further studying for the role of sotagliflozin in CVD.¹

In study 2, investigators reported that for patients with T2D, CKD, and CVD risk, sotagliflozin reduced the rate of all-cause stroke. The SCORED trial was a double-blind, randomized study of these patient populations. Treatment was randomized between the placebo and sotagliflozin, with a median follow-up time of 16 months. The outcomes of interest included all-cause stroke, defined as ischemic, hemorrhagic, mixed, or undetermined stroke type, and cause-specific stroke, according to the abstract authors.²

Investigators included 10,584 individuals with 213 all-cause stroke events, 13.6% of which were fatal. The results showed that sotagliflozin reduced the rate of all cause stroke by 34%, equating to 1.2 events per 100 patient-years compared to 1.8 evens per 100 patient-years with the placebo.²

For ischemic stroke, sotagliflozin reduced the rate by 32%, equating to 0.8 events per 100 patient-years compared to 1.2 events per 100 patient-years in the placebo group. Investigators reported that there were normal reductions for hemorrhagic stroke compared to the placebo.²

References

1. Stanger L, Holinstat M, Rickenberg A, Yalavarthi P, Yamaguchi A, Pitt B. 1065-07 – sotagliflozin, a first-in-class SGLT1/2 inhibitor, inhibits clotting potential in the vessel via inhibition of platelet activation, integrin activation, and aggregation in human platelets. American College of Cardiology. April 7, 2024. Accessed April 5, 2024. https://www.abstractsonline.com/pp8/#!/10973/presentation/11247

2. Aggarwal R, Bhatt DL, Szarek M, Davies M, Banks P, Pitt B, Steg PG. 1116-05 – sotagliflozin reduces stroke outcomes in patients with diabetes and chronic kidney disease. American College of Cardiology. April 8, 2024. Accessed April 5, 2024. https://www.abstractsonline.com/pp8/#!/10973/presentation/12628