Sodium-glucose cotransporter-2 inhibitors in cancer patients with type 2 diabetes and established immune checkpoint inhibitor-related cardiotoxicity: a retrospective analysis.

BACKGROUND

Immune checkpoint inhibitors (ICIs) significantly improve cancer prognosis but are associated with the risk of immune checkpoint inhibitor-related cardiotoxicity (iRCs), a life-threatening complication. Type 2 Diabetes Mellitus (T2DM) further increases the risk of iRCs and worsens outcomes in these patients. Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) confer cardioprotective and potential antitumor effects, their prognostic value in cancer patients with T2DM and established iRCs remains unknown.

OBJECTIVE

To investigate the association of SGLT2i use with all-cause mortality, iRCs severity, and major adverse cardiovascular events (MACE) in cancer patients with T2DM who developed iRCs during ICI therapy.

METHODS

In this retrospective study, we analyzed 98 cancer patients with T2DM and established iRCs between January 2019 and June 2025. Participants were categorized into an SGLT2i group (n = 26) and a non-SGLT2i group (n = 72). The primary endpoint was all-cause mortality; secondary endpoints included 40-day MACE and iRCs severity. Survival analyses were performed using Kaplan-Meier curves with the log-rank test. Independent associations were assessed via Cox proportional hazards regression.

RESULTS

Median follow-up was 950.5 days. SGLT2i use was independently associated with reduced all-cause mortality (adjusted HR = 0.520, 95% CI: 0.285-0.947, p = 0.033). The SGLT2i group exhibited a longer median survival time (743 days vs. 494 days) and consistently higher 1-, 2-, and 3-year survival rates (73.1% vs. 60.6%; 51.5% vs. 26.4%; 31.2% vs. 8.8%) compared to the non-SGLT2i group. Additionally, the SGLT2i group had a significantly lower proportion of high-grade iRCs (19.2% vs. 45.8%, p = 0.031). Although the incidence of MACE did not differ significantly between groups (19.2% vs. 33.3%, p = 0.271), univariate Cox regression indicated a 47% lower risk of MACE in the SGLT2i group (HR = 0.531, 95% CI: 0.202-1.391, p = 0.198), with numerical reductions observed for both overall MACE and its individual components.

CONCLUSION

SGLT2i use in cancer patients with T2DM and established iRCs was independently associated with lower all-cause mortality and linked to a reduced incidence of high-grade iRCs and favorable MACE trends. These findings warrant prospective validation to confirm cardioprotective and potential oncologic benefits of SGLT2i in this high-risk population.