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SGLT2 Inhibitors Linked to Improved Outcomes in ATTR Amyloidosis With Cardiomyopathy
Justin Riley Lam, MD, discussed findings from a retrospective cohort analysis at the 2025 ACP Internal Medicine Meeting.
Although sodium-glucose cotransporter 2 (SGLT2) inhibitors have become a mainstay in managing heart failure with preserved and reduced ejection fraction, patients with cardiac transthyretin (ATTR) amyloidosis are often excluded from clinical trials assessing these agents. Recent ACC/AHA guidelines do not address SGLT2 use in this population, leaving a gap in clinical guidance.
Justin Riley Lam, MD, medical resident at Albert Einstein Medical Center in Philadelphia, Pennsylvania, and colleagues conducted a retrospective cohort study evaluating explored the impact of SGLT2 inhibitors on outcomes in patients with wild-type ATTR amyloidosis. Lam presented findings from the analysis at the 2025 ACP Internal Medicine Meeting in New Orleans, including lower mortality and reduced IV diuretic use among patients on SGLT2 inhibitors compared to those who were not. HCPLive spoke with Lam to learn more about the analysis.
HCPLive: Can you share some background on SGLT2 inhibitors’ use in patients with amyloidosis?
Justin Riley Lam, MD: Over the past few years, SGLT2 inhibitors have been on the rise with regard to heart failure with preserved and reduced ejection fraction. Now, if you look at the studies, they usually exclude patients with amyloid, and if we look at the most recent guidelines by the ACC/AHA, they do not reference SGLT2 inhibitors at all. So we thought, if most patients have heart failure, why aren’t we using it? They're usually already on it at that point. But looking at the data on whether it's useful or not—that’s where the shortcomings come in.
Can you discuss the analysis and its findings?
Lam: So, we did a retrospective cohort analysis. We looked at patients who were diagnosed with amyloid and split them into two groups: one on SGLT2 inhibitors and one not. Then we looked at their outcomes—how they fared on the drug versus off the drug. The data are really interesting. Patients who were on it had a much lower rate of death compared to those who were not. But again, with a retrospective cohort analysis, you can only infer so much. Right now, there’s really not much out there, so I think this is the best we could have done at this point.
We saw that patients who were on SGLT2 inhibitors had a lower mortality rate compared to patients not on it. We also noted that they had a lower rate of using IV diuretics, which we used as a surrogate marker for hospitalizations, since we couldn’t use hospitalizations as an outcome in our database.
But we also have to think about limitations. Patients on SGLT2 inhibitors are usually more health literate—they may have more follow-ups, better health behaviors, and even higher socioeconomic status. As we all know, the medication can be slightly expensive, so patients on it might have better access to care. Those are factors to consider.
And of course, using ICD-10 codes and a database introduces a lot of potential misclassification errors and confounding biases that might not be reflected in the study. But overall, the data looks great. Most people with amyloid already have heart failure, so they’re usually on it already, which is a good thing. With recent studies supporting use in both preserved and reduced ejection fraction, it gives us a better shot at treating this condition.
Is there further research that you'd like to pursue?
Lam: With regard to possibly pursuing a trial, we know that most patients with cardiac amyloid present with heart failure, and by that time, they’re already on the medication. I think it would be a disservice to seek people out and not put them on it—versus just giving them access to a very effective drug. So that’s one challenge with running a trial.
As for further studies, maybe we could classify which specific SGLT2 inhibitor is more helpful. There are a few on the market right now. A subgroup analysis might be useful, and we could explore how the mechanism of action plays a role in amyloid—whether it affects the heart directly or acts more through diuresis and heart failure management. One could be independent of the other. So those are things we might want to look into in the future.
This transcript has been edited for clarity.
