SGLT2 Inhibitors Improve Survival in Cancer Patients with T2DM and ICI-Related Cardiotoxicity

Overview

This retrospective study found that sodium-glucose cotransporter-2 inhibitors (SGLT2i) use in cancer patients with type 2 diabetes mellitus (T2DM) experiencing immune checkpoint inhibitor-related cardiotoxicity (iRCs) was associated with significantly reduced all-cause mortality and lower severity of cardiotoxicity. Although major adverse cardiovascular events (MACE) incidence was not statistically different, trends favored SGLT2i use.

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can cause immune-related cardiotoxicity (iRCs), a serious complication with high mortality. Patients with T2DM are at increased risk for iRCs and worse outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardioprotective effects and potential antitumor activity, but their impact on cancer patients with T2DM and established iRCs has not been previously studied. This study addresses this gap by evaluating SGLT2i effects on survival and cardiovascular outcomes in this high-risk population.

Data Highlights

Key Findings

• SGLT2i use was independently associated with a 48% reduction in all-cause mortality (adjusted HR = 0.520, p = 0.033).
• Median survival was longer in the SGLT2i group (743 days) compared to non-users (494 days).
• The SGLT2i group had significantly fewer patients with high-grade iRCs (19.2% vs. 45.8%, p = 0.031).
• Although MACE incidence was not statistically different, there was a numerical 47% lower risk of MACE in the SGLT2i group (HR = 0.531, p = 0.198).
• Survival rates at 1, 2, and 3 years were consistently higher in patients receiving SGLT2i.

Clinical Implications

These findings suggest that SGLT2 inhibitors may offer cardioprotective benefits and improve survival in cancer patients with T2DM who develop ICI-related cardiotoxicity. Clinicians should consider the potential advantages of SGLT2i in managing this high-risk population, although prospective studies are needed to confirm these results. Integrating SGLT2i into treatment regimens may help mitigate cardiotoxicity severity and improve long-term outcomes.

Conclusion

SGLT2i use in cancer patients with T2DM and established iRCs is associated with improved survival and reduced cardiotoxicity severity. These promising results highlight the need for prospective validation to establish SGLT2i as a targeted therapeutic strategy in this vulnerable group.

Related Resources & Content

1. Perelman et al. 2023 -- SGLT2i Use and Mortality in T2DM Patients Receiving ICIs
2. 2022 ESC Cardio-Oncology Guidelines