Association of SGLT2 Inhibitor Use with Clinical Outcomes in Patients Receiving Immune Checkpoint Inhibitors: A Pan-Tumor Propensity-Matched Analysis

Background Recently, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as a treatment option for type 2 diabetes mellitus (T2DM) and have also shown promising anti-tumor activity in preclinical models. Limited clinical data exist regarding the use of SGLT2i in patients with metastatic solid tumor malignancies treated with immune checkpoint inhibitors (ICIs). Patients and Methods A retrospective, multi-center, matched cohort analysis of patients with a diagnosis of either T2DM and/or congestive heart failure and an advanced solid tumor malignancy treated with ICIs was performed using the Epic Cosmos database. Ten different solid tumor types, eleven ICIs, and three SGLT2i were analyzed. Patients in the exposure group also received an SGLT2i and had at least one overlapping cycle with ICI. Results Of the 1,146 patients included, 573 patients received SGLT2i+ICIs and 573 received ICIs alone. Compared to patients treated with ICIs, individuals who received SGLT2i+ICIs had improved median overall survival (mOS) (27.4 vs. 17.4 months, hazard ratio (HR) 0.68, log-rank test, p < 0.001). When stratified by histology, significant improvements in mOS were seen for non-small cell lung cancer and renal cell carcinoma patients. Survival benefit was attenuated when accounting for immortal time bias in late initiators of SGLT2i, though persisted among patients prescribed SGLT2i at or prior to initiation of ICI. Patients in the exposure group experienced longer time on immunotherapy compared to the control group. Conclusion Patients prescribed SGLT2i at or prior to ICI initiation had a modest improvement in survival compared to patients treated with ICIs alone. SGLT2i may be a beneficial adjunctive therapy in patients treated with ICI, though further studies are needed.