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Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer, and type 2 diabetes mellitus (T2DM) is a common comorbidity in COPD patients. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have pleiotropic effects beyond glucose lowering. However, their association with lung cancer risk in patients with COPD and T2DM remains uncertain.

Is SGLT2 inhibitor initiation associated with a lower risk of incident lung cancer in patients with COPD and T2DM?

We conducted a nationwide population-based cohort study using the National Health Insurance Database, including adults aged ≥40 years with COPD and T2DM who initiated SGLT2 inhibitors or sulfonylureas between September 2014 and December 2023. The primary outcome was incident lung cancer. Secondary outcomes included severe COPD exacerbation and all-cause mortality.

Among 14,927 patients (5,651 SGLT2 inhibitor initiators and 9,276 sulfonylurea initiators), 234 incident lung cancer events occurred during a median follow-up of 2.97 years. The 4-year cumulative incidence of lung cancer was 1.6% in the SGLT2 inhibitor group and 2.7% in the sulfonylurea group. Initiation of SGLT2 inhibitors was associated with a lower risk of incident lung cancer compared with sulfonylureas (IPTW HR 0.73; 95% CI, 0.60-0.90). SGLT2 inhibitor use was also associated with reduced risks of severe COPD exacerbation (IPTW HR 0.77; 95% CI, 0.71-0.83) and all-cause mortality (IPTW HR 0.81; 95% CI, 0.75-0.88).

In this nationwide cohort of patients with COPD and T2DM, initiation of SGLT2 inhibitors was associated with lower risks of lung cancer, COPD exacerbation, and all-cause mortality compared with sulfonylureas.