Sotagliflozin Reduces MACE Risk in Diabetic, Kidney Disease Patients in SCORED Trial

Study author Deepak L. Bhatt, MD, MPH, discusses the unique SGLT-1 and SGLT-2 inhibition derived from sotagliflozin, and how impactful its benefit may be.

New secondary analysis data from the SCORED trial show SGLT-1 and SGLT-2 inhibitor sotagliflozin was associated with significantly reduced cardiovascular death, myocardial infarction (MI), and stroke in patients with diabetes plus chronic kidney disease (CKD).

The findings, presented by Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs, at the American College of Cardiology (ACC) 2022 Scientific Sessions this weekend, raised questions regarding the clinical benefit of SGLT-1 inhibition in reduced major adverse cardiovascular events (MACE) relative to standard-care SGLT-2 inhibitors.

In an interview with HCPLive during ACC 2022, Bhatt detailed the unique characteristics of SGLT-2 and SGLT-1 inhibition: the former is expressed in the kidney, while the latter is expressed in both the kidney and the gut—meaning gut inhibition can lead to slowed glucose absorption.

“So in addition to the benefits in the kidney with respect to glucose uptake, there’s also benefits in the gut with the SGLT-1 inhibition added to SGLT-2,” Bhatt said. “So that’s sotagliflozin.”

Bhatt shared his key takeaways from the 10,000-patient SCORED trial analysis, which stratified patient data by presence of baseline cardiovascular disease (CVD) but nonetheless came away with significant benefits associated with sotagliflozin.

“We’re seeing a benefit in reducing MI and stroke, both fatal and non-fatal, that is occurring in the high-risk patients that we studied in SCORED that had a history of cardiovascular disease, but even—interestingly, surprisingly—in the lower-risk patients who didn’t have a history of CVD,” Bhatt explained.

He also highlighted the timeliness and durability of the novel dual-pathway-targeting agent in treated SCORED patients.

“What was interesting beyond that was there was a significant reduction in MACE—and it occurred pretty early,” Bhatt said. “By about 3 months, it was a significant difference, and the reduction was not only in myocardial infarction but also in stroke, which hasn’t been seen with any of the other SGLT-2 inhibitor trials to date.”

Further assessment is necessary to interpret the impact of SGLT-1 versus SGLT-2 inhibition in reducing MACE risk, but Bhatt and colleagues are not only focused on sotagliflozin. As he noted, the ongoing EMPA-KIDNEY trial will interpret the kidney disease progression, heart failure event, and MACE risk reduction derived from SGLT-2 inhibitor empagliflozin.

The results may help better define the capability of sotagliflozin.

“If it shows a reduction in MACE, then I’d have to say this is a class effect for SGLT-2 inhibitors as well, and what we saw in SCORED in terms of MACE reduction wasn’t the SGLT-1 but rather that we studied a population that was just the right combination,” Bhatt said. “If EMPA-KIDNEY doesn’t show any sort of effect on MI or stroke, then I’d say, yeah, there really is something to this SGLT-1 inhibition."

The study, "Effect of Sotagliflozin on CV and Renal Events in Patients with CV Risk, T2DM, and Renal Impairment," was presented at ACC 2022.