Weight change and Impact on prognosis in patients with Advanced Non-small Cell Lung Cancer with Concomitant diabetes mellitus treated with SGLT2 inhibitors

Abstract Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are commonly used to manage diabetes and are known to cause weight loss. This study aimed to clarify whether SGLT2i-induced weight loss influences survival or toxicity during chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and comorbid diabetes. Methods: We conducted a retrospective analysis of patients with advanced NSCLC and diabetes who received first-line chemotherapy. Patients with an Eastern Cooperative Oncology Group performance status (PS) ≥ 3 or higher, driver mutations, interstitial lung disease, untreated diabetes, or missing data were excluded. We compared weight changes, progression-free survival (PFS), overall survival (OS), and adverse events between patients with and without SGLT2i. We defined cachexia as either 5% or more body-weight loss within six months prior to the initiation of lung cancer treatment or weight loss greater than 2% and a body-mass index (BMI) of less than 20 kg/m². Results: Eighteen patients (21.9%) out of 82 received SGLT2i for diabetes. There was no difference in the incidence of cachexia between the two groups (66.7% vs. 46.9%, p = 0.184), despite significant weight loss in the SGLT2 group compared to the non-SGLT2 group (median − 5.8% vs. −3.4%, p = 0.039). No significant differences were observed in progression-free survival (PFS) (median 6.2 vs. 4.1 months, p = 0.512) or overall survival (OS) (median 11.9 vs. 14.6 months, p = 0.583). Grade ≥ 3 adverse events occurred in 11.1% of patients in the SGLT2i group and 31.2% of patients in the non-SGLT2i group (P = 0.132). There were no cases of diabetic ketoacidosis or urinary tract infections. Conclusion: SGLT2 inhibitors were associated with weight loss and were not associated with worse survival or increased toxicity in this retrospective cohort.