Rahul Aggarwal, MD: Efficacy of Sotagliflozin Independent of Baseline A1c

Rahul Aggarwal, MD

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New research suggests the efficacy of sotagliflozin on heart-failure related outcomes is independent of baseline hemoglobin A1c (HbA1c).¹

The data, presented at the 83rd Scientific Sessions of the American Diabetes Association (ADA 2023), showed sotagliflozin reduced the risk of cardiovascular death and heart failure-related events across patients in both the SOLOIST-WHF and SCORED trials (P for treatment <0.0001) with a range of baseline A1C values.

At ADA 2023, the HCPLive editorial team spoke with presenting investigator Rahul Aggarwal, MD, a cardiology fellow at Brigham and Women's Hospital, Harvard Medical School, on the study’s findings and its implication for treatment.

Can you elaborate on the goal of your analysis and what your investigative team set out to find?

Thanks again for having me. So, what our study looks at is a question actually very important to a lot of endocrinologists and primary care physicians. And that there is a lot of wonderful data about sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with diabetes.

But the question is, does the effect of these agents vary by their HbA1c? So, for those that have worse A1c, or better, controlled A1c, does the effect of these agents vary? And so that’s the kind of primary information that our analysis is set up to look at.

What did the analysis find and how does it better our understanding of the therapy class?

So, when we look at sotagliflozin, which is a combined SGLT1, SGLT2 inhibitor, we saw with sotagliflozin is that irrespective of the baseline HbA1c, patients had similar reductions in cardiovascular death, heart failure hospitalization, and heart failure outcomes. What this tells us is that for individuals with diabetes, who are considering SGLT2 inhibitors, using them irrespective of baseline HbA1c, we’ll be able to see those beneficial outcomes in these patients.

How does the FDA labeling underscore score the up-titration of the therapy in-hospital?

That’s an excellent question. So, sotagliflozin, as you may be aware, recently got FDA approval last month.² And interestingly, it was actually approved with a very broad label because of the trials that looked at sotagliflozin. And it is recommended in patients irrespective of heart failure ejection fraction and it’s recommended on a broad spectrum of patients. So, I think the labeling is actually quite broad, and it will allow for use in a lot of individuals and allow for beneficial effects for these outcomes that I mentioned.

Looking at the recent approval, how has it changed the treatment landscape? What are the larger benefits of having another tool for treatment?

I think one of the major things for the SGLT2 inhibitors is that certain agents may be better suited for certain patients. To have more options allow individuals and clinicians to have more tools in their tool kit to help patients and this can play out in multiple different ways. Sometimes insurance will only take one agent over the other, sometimes the patients will only tolerate one agent or the other. And when we’ve seen that the beneficial effects are quite large, we saw a 25% reduction in the outcomes, that when the beneficial effect is that large, having multiple options allows us to maximize therapy for these individuals that need it.

What else would you want to know or better understand about sotagliflozin’s role in treatment?

I think one of the things that for SGLT inhibitors, in general, we don’t fully understand that we want to better understand is what is their mechanism for improvement in these heart failure outcomes. Initially, these drugs were developed for diabetes, and they were developed to reduce hemoglobin A1c. But, a lot of the evidence and landscape now point out that the effect on heart failure outcomes is independent of the A1c or blood glucose pathway. So, what we’re very curious in is what is the mechanism that these SGLT inhibitors improve these outcomes outside of the blood glucose pathways.

Aggarwal reports no relevant disclosures.

References

1. Bhatt DL, Szarek M, Davies MJ, Banks PL, Pitt B, Steg PG. The Efficacy of Sotagliflozin on Heart-Failure Related Outcomes Is Independent of Baseline A1C. Oral presentation at the 83rd Scientific Sessions of the American Diabetes Association. June 23 – 26, 2023.
2. Campbell P. FDA approves Sotagliflozin for treatment of heart failure. HCP Live. May 26, 2023. Accessed June 25, 2023. https://www.hcplive.com/view/fda-approves-sotagliflozin-for-treatment-of-heart-failure.