Efficacy and Safety of Sodium-Glucose Co-Transporter-2 Inhibitors in Cancer Patients with Diabetes Mellitus

Background: Diabetes mellitus (DM) and cancer exhibit a high likelihood of co-occurrence. DM serves as a risk factor for various forms of cancer and is associated with poorer prognosis. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective antidiabetic therapies associated with reduced all-cause mortality in the general population; however, data among the cancer population are scarce.

Objective: We aimed to assess the efficacy and safety of SGLT2i therapy among patients with DM and cancer.

Methods: A large retrospective, single-center study including 849 patients diagnosed with DM and active cancer. Patients were divided into two groups: 169 patients treated with SGLT2i before cancer diagnosis (SGLT2i) and 680 patients SGLT2i naive (non-SGLT2i). The primary endpoint was all-cause mortality. The secondary endpoint was the composite of cardiovascular (CV) outcomes, including heart failure (HF), acute coronary syndrome (ACS), and arrhythmias.

Results: After a median follow-up of 48 months [IQR 27, 72], all-cause mortality was significantly lower in the SGLT2i group (67% vs. 53%, p=0.001). Multivariable Cox regression identified SGLT2i as an independent predictor of reduced all-cause mortality (HR 0.676 [95% CI 0.532-0.860], p=0.001). CV outcomes were higher in the SGLT2i group (28% vs 16%, P=0.001), driven by increased HF exacerbations (14% vs. 7%, p=0.008). After propensity score matching, SGLT2i remained a significant predictor for reduced mortality (p=0.016), with no significant differences in CV outcome (p=0.067).

Conclusions: SGLT2i was associated with lower all-cause mortality in patients diagnosed with DM and cancer. Randomized clinical trials are needed to confirm these findings and explore the underlying mechanism