SGLT2 inhibitors, a class of FDA-approved anti-diabetes medications, may slow the progression of in situ pulmonary adenocarcinoma and reduce the need for surgical interventions, according to a new study.
In situ and early-stage cancers are the fastest-growing lung cancers and are often found incidentally on computed tomography (CT) scans as ground glass opacities and small pulmonary nodules. Patients with these lesions are often followed expectantly and tend to need surgery eventually. Emerging evidence indicates that the glucose transporter sodium-glucose cotransporter 2 (SGLT2) is involved in early adenocarcinoma development.
SGLT2 Inhibitor Therapeutic Potential
The researchers identified diabetic patients with a lung nodule confirmed on at least two serial CT scans between 2014 and 2024. Investigators compared patients who were prescribed an SGLT2 inhibitor with similar patients who received an alternative class of anti-diabetic medication.
Using multivariable adjusted Cox regression models and log-rank testing, the researchers examined the incidence of lung nodule growth and the time to intervention. They considered lung nodule growth to be an increase in size of more than 2 mm or the growth or development of a solid component, which would suggest invasive disease. Interventions included biopsy, resection, empiric radiotherapy, and chemotherapy.
Of the 218 adult diabetic patients who were diagnosed with a lung nodule, 109 patients were prescribed an SGLT2 inhibitor, and 109 received an alternative diabetic medication. Both groups were similar in demographics, including sex, race, and smoking history. Mean HbA1c was slightly higher in the SGLT2 inhibitor group vs the alternative medication group (7.7 vs 7.1, respectively; P<0.01).
The study team followed participants in both groups for similar lengths of time. Patients who received an SGLT2 inhibitor were significantly less likely to have detectable lung nodule growth than were those who received alternative diabetic medications (13.8% vs 25.7%, respectively; P=0.04).
Patients taking an SGLT2 inhibitor were less than half as likely to undergo a surgical intervention than those on alternative diabetic medications, with a 5.5% cumulative incidence of surgical interventions in the SGLT2 inhibitor group versus 11.9% in the alternative diabetic medications group (HR 0.15; 95% CI, 0.02-0.77; P=0.048). The number needed to treat with an SGLT2 inhibitor to prevent one additional surgical intervention over 10 years was 15.6 patients.
The researchers note in their abstract that SGLT2 inhibitors’ therapeutic potential for early-stage pulmonary adenocarcinoma may also have broad implications for other early-stage adenocarcinomas of various tumor types. They recommend prospective studies to confirm these results.
Reference
Welch K, McGovern, K, Chen L, et al. Sodium-Glucose Cotransporter 2 Inhibitors Attenuate Growth and Decrease Surgical Interventions on In-Situ Pulmonary Adenocarcinoma. Presented at: CHEST 2025, October 19-22, 2025; Chicago.
