Fact checked byRichard Smith

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September 23, 2024
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SGLT2s could prevent cardiotoxic effects of cancer therapies in patients with diabetes

Fact checked byRichard Smith
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Key takeaways:

  • SGLT2 inhibition may improve CV outcomes in patients with diabetes undergoing cancer therapy.
  • The cardioprotective effect was particularly strong for patients taking empagliflozin.

SGLT2 inhibition may prevent cancer therapy-related cardiac dysfunction and improve other outcomes in patients with diabetes undergoing cancer therapy, researchers reported.

An analysis of the effects various SGLT2 inhibitors on CV outcomes in patients with cancer undergoing treatment who had diabetes but no history of cardiomyopathy or HF was presented at the Global Cardio Oncology Summit and simultaneously published in JACC: CardioOncology.

woman receiving chemotherapy
SGLT2 inhibition may improve CV outcomes in patients with diabetes undergoing cancer therapy. Image: Adobe Stock

Patients with cancer are a high-risk population for CVD and, as such, efforts need to be made to not only treat their CVD but also try to prevent it in the first place. With the amazing advancement that we have experienced in oncology care and patient survivorship, there is also a risk that these patients can develop cancer therapy-related cardiac dysfunction,” Sarju Ganatra, MD, FACC, medical director of sustainability and director of the cardio-oncology program at Lahey Hospital & Medical Center, Beth Israel Lahey Health in Burlington, Massachusetts, told Healio. “The clinical implications of this entity can be substantial, including premature termination of cancer therapy and, hence, increased risk of disease-related morbidity and mortality. Interest has henceforth mounted to effectively target cancer cells while minimizing adverse effects on the CV system. While various agents have been tested, to date, no other treatment has been demonstrated to be very effective and safe in preventing cancer therapy-related cardiac dysfunction.”

Sarju Ganatra

Using the TriNetX database, Ganatra and colleagues conducted a retrospective analysis of 8,675 adult patients with diabetes and cancer treated with cardiotoxic therapies and no history of cardiomyopathy or HF (mean age, 65 years; 42% women; 71% white). Patients were stratified by SGLT2 inhibitor use and outcomes were compared during a 12-month follow-up period.

The most common malignancy in this cohort was breast cancer (26.3%), followed by lymphomas (20.8%), gastrointestinal cancer (18.9%), metastatic malignancy (16.4%) and multiple myeloma and myelodysplastic syndromes (12.8%).

The most common anticancer therapy used was anthracyclines (24.5%), followed by monoclonal antibodies (21.2%), antimetabolites (19%), small molecule tyrosine kinase inhibitors (16.9%), proteasome inhibitors (8.3%), alkylating agents (7.2%) and aromatase inhibitors (3%).

After propensity-score matching patients taking an SGLT2 inhibitor with those not taking one, the researchers reported that those prescribed an SGLT2 inhibitor had lower risk for cancer therapy-related cardiac dysfunction (HR = 0.76; 95% CI, 0.69-0.84), HF exacerbations (HR = 0.81; 95% CI, 0.72-0.9), all-cause mortality (HR = 0.67; 95% CI, 0.61-0.74) and all-cause hospitalizations and ED visits (HR = 0.93; 95% CI, 0.89-0.97) compared with patients not on SGLT2 inhibitors.

Additionally, the benefits of SGLT2 inhibition in this patient population were consistent across all cancer therapies included in the analysis.

“Some preclinical and smaller limited clinical studies where patients are getting one type of chemotherapy have demonstrated that SGLT2 inhibitors can be effective in preventing cardiotoxicity,” Ganatra told Healio. “However, we are incredibly pleased to demonstrate that it works in preventing cardiotoxicity among patients receiving a wide range of potentially cardiotoxic cancer therapies. This has been demonstrated for the first time and we believe it sets the stage for further prospective studies to help this vulnerable patient population and possibly offers them a preventive strategy.”

Among SGLT2 inhibitors, empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) was associated with a greater treatment effect for reducing risk for cancer therapy-related cardiac dysfunction (HR = 0.78; 95% CI, 0.7-0.87; P < .001) compared with dapagliflozin (Farxiga, AstraZeneca; HR = 0.93; 95% CI, 0.79-1.11; P = .45) and canagliflozin (Invokana, Janssen; HR = 0.92; 95% CI, 0.77-1.11; P = .41), according to the study.

“This finding in our study could be a result of small sample size. However, Zhang et al also showed in their meta-analysis from 2022 that empagliflozin compared to three other SGLT2 inhibitors was associated with greater improvements in cardiac remodeling parameters. Dabour et al had commented recently on empagliflozin’s ability to improve cardiac energy metabolism, anti-inflammatory and antioxidative effects, as well as antifibrotic effects,” Ganatra told Healio. “Nonetheless, more studies are needed to further elucidate empagliflozin’s mechanism of action in this specific patient population compared to other SGLT2 inhibitors, as well as SGLT2 inhibitors as a class of cardioprotective medications for patients with cancer and cancer therapy-related cardiac dysfunction.

“While some preclinical and smaller clinical studies have shown effect of SGLT2 inhibitors in cancer treatment itself, our large real-world study further solidifies the potential anticancer beneficial effects of SGLT2 inhibitors among patients with diabetes,” he said. “Most importantly, this study further illustrates the link of metabolic disease such as diabetes with both cancer and cardiovascular disease. This highlights the need of cardio-onco-metabolics field and studies and agents that examine the effect on the entire axis.”

For more information:

Sarju Ganatra, MD, FACC, can be reached at sarju.ganatra@lahey.org.

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