A Real-World Data Assessment of Pulmonary Toxicity of Inhaled Insulin for Diabetes

Inhalation of technosphere insulin (TI) has been shown to significantly reduce postmeal glucose excursions compared with injections of rapid-acting analogue (RAA) insulin in people with diabetes. However, TI has not gained widespread use in part due to concern about pulmonary toxicity, although clinical trials have not suggested a safety signal. To evaluate the pulmonary toxicity of TI, an analysis was performed using real-world data (RWD) in the Epic Cosmos database of approximately 300 million patients.

From the Cosmos database, individuals with diabetes were identified who had at least two prescriptions for TI (cases) or RAA insulin with no TI prescriptions ("controls") between January 1, 2015, and October 8, 2024, with >365 days between the first and last prescription. The first TI or RAA prescription was considered as the index date. Exclusion criteria for selection of cases and controls included diagnoses or testing suggesting increased risk of pulmonary disease prior to or within 1 year postindex date. Controls were matched 3:1 to cases on a variety of factors. Outcomes were assessed for diagnosis codes for lung cancer, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis at least 1 year after the index date.

Inclusion criteria were met for 647 cases, which were matched to 1830 controls. Beginning 1 year postindex date, a lung cancer diagnosis was recorded in no cases and in two controls (0.11%), while a diagnosis of COPD, emphysema, or chronic bronchitis was recorded in 1 (0.16%) case and in 27 (1.48%) controls (odds ratio = 0.107, 95% CI: 0.014-0.787, P = 0.007).

While there are limitations to the interpretation of results from a study using RWD, it is reassuring that there was no increase in pulmonary toxicity attributable to inhaled TI for treatment of diabetes with respect to lung cancer, COPD, emphysema, and chronic bronchitis.