SGLT2 inhibitor use reduces progression and surgical intervention of persistent pulmonary nodules

OBJECTIVE: In-situ and early-stage cancers are the fastest growing subset of pulmonary malignancies, often presenting as persistent nodules and ground glass opacities. These lesions are frequently surveilled, though many progress and require interventions. We hypothesized that sodium-glucose cotransporter-2 inhibitors (SGLT2i) may slow progression of early pulmonary malignancy. METHODS: In this retrospective cohort study of 6,362 patients, 200 adults with type 2 diabetes mellitus (T2DM) and a pulmonary nodule suspicious for lung cancer were matched based on exposure to an SGLT2i or an alternative T2DM medication. Primary outcomes included nodule progression (growth > 2 mm or solid component development) and need for intervention (biopsy, surgery, radiotherapy, or chemotherapy). Multivariable Cox regression and log-rank tests were used for analysis. RESULTS: The SGLT2i and non-SGLT2i groups had similar comorbidity profiles, initial nodule sizes and surveillance durations. After a median follow-up of 28 months (range: 3-125), 12% in the SGLT2i group versus 24% in the non-SGLT2i group had progression (p = 0.04). Adjusting for covariates, SGLT2i use was associated with reduced risk of nodule progression (HR = 0.38, 95% CI: 0.18-0.80) and longer mean time to progression (37.7 versus 29.2 months). Surgical intervention was less frequent in the SGLT2i group (3% versus 13%, p < 0.01), with prolonged time to intervention (HR: 0.18, 95% CI: 0.07-0.47). CONCLUSION: SGLT2i use was associated with lower risk of pulmonary nodule progression and surgical intervention among patients with T2DM, independent of comorbidities, glycemic control, and baseline nodule size. These findings suggest a potential role for SGLT2i in reducing growth of persistent pulmonary nodules.