Real-World Incidence of Lung Malignancy and Chronic Obstructive Pulmonary Disease with Inhaled Insulin in People with Diabetes

Objective: Inhaled insulin offers an alternative to subcutaneous administration, although concerns remain regarding pulmonary risks. We assessed the real-world safety of inhaled insulin versus rapid-acting analogue (RAA) insulin on lung malignancy and chronic obstructive pulmonary disease (COPD) in adults with diabetes. Materials and Methods: This retrospective cohort study used the TriNetX Network to evaluate risk of lung malignancy and COPD in adults with type 1 or type 2 diabetes prescribed either inhaled insulin or RAA insulin. Results: After propensity score matching, between the inhaled insulin versus RAA insulin cohorts there was no difference in risk of any lung cancer ( n ≤ 10/2530 vs. n ≤ 10/2531, risk ratio [RR] = 1; 95% confidence interval [CI]: 0.42, 2.40, P = 0.999). The risk of developing the composite COPD outcome was greater in the inhaled insulin cohort versus the RAA insulin cohort ( n = 41/2493, risk 1.6% vs. n = 12/2514, risk 0.5%; RR = 3.45; 95% CI: 1.82, 6.54, P < 0.001). Conclusions: No association was found between inhaled insulin and any lung malignancy. Inhaled insulin was associated with a threefold increase in COPD versus RAA although the absolute risk was low. The biological plausibility of this association is not definitive. Given the retrospective design and potential for ascertainment bias, causal inference is limited although findings underscore the need for continued evaluation of inhaled insulin’s pulmonary safety.