{
  "abstract": "Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular and renal benefits in patients with metabolic diseases, but their role in oncology is less established. Preclinical data suggest SGLT2 inhibitors may enhance immunotherapy efficacy by modulating tumor metabolism, reducing inflammation, and attenuating the Warburg effect. 1 However, real-world evidence evaluating their impact on survival and renal outcomes in patients with solid tumors receiving immune checkpoint inhibitors (ICIs) is lacking.Methods This retrospective cohort study utilized deidentified electronic health record data from the TriNetX Research Network, encompassing 103 healthcare organizations. Adults (≥18 years) with melanoma, lung cancer, or genitourinary (GU) malignancies who initiated ICIs were included. Patients were excluded if they lacked follow-up or complete medication data. The exposure group consisted of patients receiving any SGLT2 inhibitor prior to ICI initiation. Propensity score matching (1:1) was performed to balance demographics, comorbidities, cancer therapies, and medications. The primary outcome was all-cause mortality. Secondary renal outcomes included acute kidney injury (AKI), dialysis, and kidney biopsy. Time-to-event outcomes were assessed using Kaplan-Meier survival and Cox proportional hazards models. Binary outcomes were compared using risk ratios (RRs) with 95% confidence intervals (CIs).Results After matching, 4,708 patients (mean age 69.1 years; 70.0% male) were included (2,354 per group) ( Table 1). SGLT2 inhibitor use was associated with significantly lower all-cause mortality (26.8% vs. 45.3%; RR 0.592; 95% CI, 0.547–0.642; HR 0.753; 95% CI, 0.682–0.831). Median survival was longer in the SGLT2i group (1,604 vs. 1,035 days). AKI incidence was lower in the SGLT2i group (20.0% vs. 26.6%; RR 0.752; 95% CI, 0.665–0.851), as were kidney biopsy rates (1.1% vs. 2.3%; RR 0.481; 95% CI, 0.303–0.766). Dialysis initiation incidence was lower but not statistically significant (0.9% vs. 1.4%). Subgroup analysis showed consistent mortality benefit in thoracic cancers and notable renal protection in GU cancers (figure 1).Conclusions Among patients with solid tumors treated with ICIs, concurrent SGLT2 inhibitor use was associated with improved overall survival and reduced risk of renal complications. These findings support further investigation of SGLT2 inhibitors as adjunctive agents in immuno-oncology, particularly for their potential to mitigate immunotherapy-related toxicity while enhancing therapeutic benefit. Prospective studies are warranted to confirm causality and explore underlying mechanisms of action.Reference Pliszka M, Szablewski L. Glucose Transporters as a target for anticancer therapy. Cancers. 2021;13:4184.Abstract 1071 Table 1Baseline demographic, clinical, and treatment characteristics of propensity matched cohorts receiving immune checkpoint inhibitors with or without concurrent SGLT2 inhibitor useAbstract 1071 Figure 1Risk ratios for adverse kidney and mortality outcomes with SGLT2 inhibitor use among cancer patients receiving immune checkpoint inhibitors, stratified by cancer type. Forest plots display risk ratios (RR) with 95% confidence intervals for AKI), dialysis, kidney biopsy, and all-cause mortality. Subgroup-specific estimates are shown for genitourinary, thoracic, and melanoma cohorts, with overall pooled effects labeled",
  "authors": [
    {
      "affiliations": [
        "University Hospitals/Case Western Reserve University, University Heights, OH, USA"
      ],
      "name": "Alex J Carsel"
    },
    {
      "affiliations": [
        "University Hospitals/Case Western Reserve University, Cleveland, OH, USA"
      ],
      "name": "Arash A Rashidi"
    },
    {
      "affiliations": [
        "Case Western University, Cleveland, OH, USA"
      ],
      "name": "Jaime A Perez"
    },
    {
      "affiliations": [
        "Case Western University, Cleveland, OH, USA",
        "University Hospitals Seidman Cancer Center, Cleveland, OH, USA"
      ],
      "name": "Qian Wang"
    },
    {
      "affiliations": [
        "University Hospitals Seidman Cancer Center, Cleveland, OH, USA",
        "Case Western Reserve University, Westlake, OH, USA",
        "University Hospitals Cleveland Medical Center, Cleveland, OH, USA"
      ],
      "name": "Ankit Mangla"
    }
  ],
  "title": "1071 SGLT2 inhibitor use and survival in solid tumors treated with immune checkpoint inhibitors: a real-world cohort study",
  "uid": "cdee7daa-0c68-550e-8dd4-6e146a687b88"
}