Sotagliflozin SCOREs in T2D patients with kidney disease

The dual SGLT1/2* inhibitor sotagliflozin significantly lowers the risk of the composite outcome of cardiovascular (CV) deaths, hospitalizations for heart failure (HHF), and urgent visits for heart failure in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), regardless of albuminuria status, according to the SCORED trial presented at ADA 2021.

“SCORED is unique among the SGLT2i trials as it studies patient population that either has not been studied (CKD stage 4) or have been under-represented (CKD stage 3b) in other SGLT2i CV and kidney outcome trials,” explained Dr Lawrence Leiter from the University of Toronto, Toronto, Canada, who presented on the background leading to the trial during ADA.

Therefore, the data will be more generalizable because a broader range of patients with CKD were included, regardless of whether they had macroalbuminuria, he pointed out.

In the multicentre, double-blind trial, 10,584 patients (median age 69 years) with T2D and CKD (eGFR**, 25–60 mL/min/1.73 m²) were randomized 1:1 to receive sotagliflozin or placebo.

The revised primary composite endpoint of total CV deaths, HHF, and urgent HF visits were significantly reduced by 26 percent with sotagliflozin vs placebo (events per 100 patient-years, 5.6 vs 7.5; hazard ratio [HR], 0.74; p=0.0004).

“The benefit occurred very early. The curves [for the two treatment groups] separated almost immediately and the benefit of sotagliflozin became statistically significant by 95 days — at which point the HR was 0.70, with a p-value of 0.038,” reported study co-investigator Dr Mikhail Kosiborod of Saint Luke’s Mid America Heart Institute in Kansas, Missouri, US.

Due to loss of funding, the trial was stopped early and the original primary endpoints were amended to the composite outcome as above. Nonetheless, there were also robust reductions in the original coprimary endpoints of time to first MACE*** (HR, 0.84; p=0.035) and time to CV deaths or HHF (HR, 0.77; p=0.001), said Kosiborod.

“The total CV deaths, MIs, and strokes [ie, components of MACE] were reduced by 23 percent, likely due to the SGLT1 effect of sotagliflozin on MI and also stroke, [which were reduced by 32 percent and 34 percent in risk, respectively],” observed Kosiborod.

With regard to the safety profile, diarrheoa (8.5 percent vs 6.0 percent), genital mycotic infections (2.4 percent vs 0.9 percent), volume depletion (5.3 percent vs 4.0 percent), and diabetic ketoacidosis (0.6 percent vs 0.3 percent) were more common in the sotagliflozin than the placebo groups.

“[Nonetheless,] with careful patient selection, sotagliflozin was generally well tolerated,” Kosiborod stated.

“The results presented today add to the growing body of evidence demonstrating the overall benefit of this new class of glucose-lowering agents. It is now clear that most patients with T2D and either kidney disease or heart failure should be assessed for initiation of an SGLT inhibitor,” the researchers concluded.  

“As the pharmacologic inhibition by sotagliflozin is independent of insulin and does not depend on kidney function ... therefore, even in patients with impaired kidney function, sotagliflozin would still have some glucose-lowering ability,” said Leiter.

*SGLT: Sodium-glucose cotransporter

**eGFR: estimated glomerular filtration rate

***MACE: Major adverse coronary events (comprising CV deaths, nonfatal myocardial infarction, or nonfatal stroke)