Rahul Aggarwal, MD: Clinical Effect of Sotagliflozin on Heart Failure, MACE Outcomes

Rahul Aggarwal, MD

Credit: LinkedIn

A post-hoc analysis of the SCORED trial revealed clinical benefit on heart failure and atherosclerotic events with the use of sotagliflozin (INPEFA®), an oral inhibitor of sodium-glucose cotransporter types 2 and 1, in patients at high risk for cardiovascular events.¹

The data, presented at the American Heart Association (AHA) Scientific Sessions 2023 in Philadelphia, Pennsylvania, showed statistically significant risk reductions in heart failure and major adverse cardiovascular event (MACE)-related outcomes in as early as 3 months for this high-risk population.

For total cardiovascular deaths, hospitalizations for heart failure, or urgent visits for heart failure, the relative risk reduction observed in patients treated with sotagliflozin compared to placebo was 26% (P <.001). For MACE, the relative risk reduction observed in patients treated with sotagliflozin versus placebo was 23% (P < .001).

In an interview with HCPLive, presenting investigator Rahul Aggarwal, MD, a cardiology fellow at Brigham and Women's Hospital, Harvard Medical School, discussed the need for earlier initiation of sotagliflozin and an improved understanding of how the mechanisms by which the therapy improves heart failure- and MACE-related outcomes.

HCPLive: What are the primary takeaways from this analysis and how does it underline the potential role of sotagliflozin?

Aggarwal: Thank you for having me. One of the biggest points that we really wanted to get across with this analysis is the effect of sotagliflozin in reducing both heart failure outcomes and cardiovascular MACE outcomes is very rapid. We saw the effect within 90 days from a statistical significance standpoint. And so this indicates that, from a clinical standpoint, we need to be able to prescribe therapy relatively quickly, because the effects can come on very soon.

HCPLive: One of the biggest things from the SOLOIST trial, when I've spoken to investigators, is just how important that in hospital initiation was, and how safe it was for these patients. Now, we’re seeing this similarly, on a different scale, in patients with chronic kidney disease (CKD). How does this underline the need and the safety of this agent in early prescription and disease course for patients with heart failure or CKD?

Aggarwal: I think that's exactly the emphasis here is that we really need to be starting these therapies in hospital, at index admission. And the reason for this is that often it can take patients many months to have a follow up visit, it can take them many months to get on therapy. And, so, if we can start it in hospital, and we know that the therapy is both effective and safe, then we can see a lot of that benefit even before that first follow up visit even happens. Our analysis is really kind of focusing on the need for early initiation of these therapies.

HCPLive: As we look at the treatment landscape, what might be the role of sotagliflozin given the potential benefits of SGLT1 inhibition? When you decide between these therapies, how would you convey the benefit of sotagliflozin to your peers treating this patient population with diabetes.

Aggarwal: I think it’s a little bit difficult to understand exactly which effects are being driven by the SGLT2 inhibitor effects of sotagliflozin and which are being driven by the SGLT1. But I think one thing that’s clear from the outcomes studies here and in this study, is that the effects are not just for heart failure outcomes. They’re also for MACE outcomes as well. Really important endpoints form a cardiovascular standpoint, sotagliflozin showed reduction there. I think that one of the standout features of this therapy is that it’s able to improve outcomes, not just for heart failure. The question still remains to be cleared, how exactly the mechanism is and what effects does the SGLT1 have on the outcomes here. But, one thing is clear from the trials, is that the outcomes are beneficial both for heart failure and for cardiovascular outcomes.

References

1. _{INPEFA® (sotagliflozin) Use Associated with Early Clinical Benefit in Heart Failure and Atherosclerotic Events in Analysis of Clinical Data. Lexicon Pharmaceuticals. November 12, 2023. https://www.lexpharma.com/media-center/news/2023-11-12-inpefa-r-sotagliflozin-use-associated-with-early-clinical-benefit-in-heart-failure-and-atherosclerotic-events-in-analysis-of-clinical-data. Accessed November 13, 2023.}