SGLT2 Inhibitors May Not Protect Against Cardiotoxicity From Cancer Treatment: Rakendu Rajendran, MBBS

At the ASPC 2025 Congress on CVD Prevention, Rakendu Rajendran, MBBS, a third-year internal medicine resident with Virtua Health, presented the poster, “Cardiovascular Outcomes in Cancer Patients on Capecitabine or Cytarabine with Concomitant SGLT2 Inhibitor Use: A Retrospective Cohort Study.” Here she breaks down the importance of gathering more data specifically on antimetabolites and their cardiotoxic effects to see if sodium-glucose cotransporter 2 (SGLT2) inhibitors could have a positive impact.

Revisit part 1 of her interview, where she discusses sex-based differences in myocardial infarction and stroke among cannabinoid users.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

Why is it important to study interactions between antimetabolites and SGLT2 inhibitors?

SGLT2 inhibitors, in the recent past, there's been a lot of interest in this drug. It's a very growing one. There has been observed evidence for improved outcomes with patients who are diabetic, patients with heart failure, but we thought it would be interesting to study their impact on preventing or looking at the long-term outcomes of major cardiovascular event incidents in patients who get chemotherapy, since many of these drugs actually are cardiotoxic. Looking at the existing literature, the pre-existing literature, suggests that it helps reduce adverse cardiovascular events, but the evidence is more predominant, it's stronger, in cases of patients who were receiving some other drug classes compared to antimetabolites, like anthracyclines or tyrosine kinase inhibitors.

Antimetabolites, the existing data is not as robust. We thought it would be worthwhile to look into this drug class as such. It was born out of a curiosity to see if SGLT2 inhibitors will prevent heart failure in patients undergoing chemo with these drugs, because [they’re] helpful in patients with heart failure, so what if they take it along with the chemo and would it lead to improved outcomes? But surprisingly, we found out that it does not, in our study at least, but again, we looked at only 3-year outcomes, so long-term prospective data would definitely help. Again, adding a medication comes with its own risks and benefits, like potential drug interactions, and we're adding the cost and all those logistic things that go into it as well, so we want to be sure about the benefit before adding another drug.

Potential mechanisms include that this drug can cause some diuresis, cause some volume depletion, cause electrolyte abnormalities on top of the pre-existing adverse effects of these chemo drugs like nausea, vomiting, which is already making the patient dehydrated. This can exacerbate renal dysfunction, cause worse electrolyte abnormalities, which could predispose them to arrhythmias, and this could explain the increased incidence in our study, but prospective and more longer-term data are needed to confirm our findings.

It's possible that the worsening renal function could lead to accumulation of toxic metabolites of these drugs, which can further make the cardiotoxicity worse. Those are some theories, but it's worthwhile looking into prospective data.

Were there any surprises within your results?

Because we have been seeing a lot of benefit of SGLT2 inhibitors in patients with heart failure, I was curious to see if adding it to patients who undergo chemotherapy with medications that are known to cause heart failure or other cardiovascular adverse effects, was curious to see if that would prevent these outcomes or how it would help these patients. But our study, unfortunately, showed that it makes it worse in these 2 drug groups.

Pre-existing data does suggest that some of the other chemotherapy drugs, the data are more robust in patients taking some of the other chemo drugs, like tyrosine kinase inhibitors or anthracyclines, but at least when we looked at these 2 drugs, cytarabine and capecitabine, the data were not promising. It was rather the other way.