SCORED: Sotagliflozin Leads to Reductions in CV Death, MI, Stroke Regardless of CVD Presence

Updated findings from SCORED presented by Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital Heart & Vascular Center and professor of medicine at Harvard Medical School, at the American College of Cardiology’s (ACC) 70th Scientific Session offered new insights on the benefits of sotagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD).

Specifically, the treatment resulted in significantly reduced cardiovascular (CV) death, myocardial infarction (MI), and stroke in patients with and without cardiovascular disease (CVD).

Sotagliflozin is a dual sodium–glucose co-transporter-2 and 1 (SGLT2/1) inhibitor. SGLT1 functions as the primary transporter for absorption of glucose and galactose in the gastrointestinal tract, and SGLT2 is expressed in the kidney and reabsorbs 90% of filtered glucose.

In the SCORED trial, a total of 10,584 stable outpatients with diabetes and CKD were randomized to the treatment or placebo for a median of 16 months. In the current analysis, researchers assessed those with (n = 5144) and without (n = 5440) CVD at baseline to determine the drug’s effect.

Investigators found:

• In both the patients with and without CVD, there were significant reductions in CV death, MI, and stroke (HR, 0.79 and 0.74, respectively)
• Relative risk reductions were very similar in both subgroups, although the baseline rates were expectedly higher in those with CVD and the absolute risk reduction was 3 times larger
• Reductions in total MI (HR, 0.69 and 0.66) and stroke (HR, 0.69 and 0.62) were individually evident in both subgroups
• Sensitivity analyses with various post hoc definitions of CVD showed generally consistent results

Overall, a 26% reduction was seen in the treatment arm with regard to composite of total CV deaths, hospitalizations for heart failure, and urgent heart failure visits, with a very early, significant benefit seen at around 3 months.

Major adverse cardiac event benefits were seen regardless of prior coronary, cerebral, or peripheral artery disease and absence of established cardiovascular disease.

Researchers hypothesize the positive findings could be due to the drug’s unique additional SGLT1 inhibition, in contrast with other SGLT2 inhibitor trials, although “the evolution of SGLT2 inhibitors in heart failure management has been nothing short of remarkable,” Bhatt said.

Adverse events reported in SCORED included urinary tract infections, diarrhea, volume depletion and bone fractures, among others. Notably, researchers saw a significant increase in diarrhea among those taking sotagliflozin, most likely reflecting the SGLT1 inhibition in the gut, Bhatt explained.

However, proportions of serious adverse events were similar between the treatment and control arms while adverse events generally did not lead to treatment discontinuation.

As SCORED was stopped early due to COVID-19, its shortened duration limited statistical power with regard to significant reductions in CV death. This early endpoint also “limited the magnitude of absolute risk reductions in MACE [major adverse cardiovascular events],” Bhatt said.

Sotagliflozin is not yet FDA approved although it has been authorized for type 1 diabetes by the European Medical Agency. Lexicon Pharmaceuticals has filed for FDA approval in the United States.

“I hope it gets approved. I think it might be the best-in-class,” Bhatt said. “It has the heart failure benefits that other SGLT2 inhibitors have, I think that’s a class effect…I think starting it early in patients without contraindication is the right thing to do.”