Lung Cancer–Related Mortality With Inhaled Insulin or a Comparator: Follow-up Study of Patients Enrolled in Exubera-Controlled Clinical Trials (FUSE) Final Results

OBJECTIVE The Follow-up Study of Patients Previously Enrolled in Exubera-Controlled Clinical Trials (FUSE) was designed to evaluate whether patients previously treated with Exubera (EXU; insulin human [rDNA origin], inhaled powder) in controlled clinical trials died because of incident primary lung cancer at a substantially higher rate than patients treated with a comparator. RESEARCH DESIGN AND METHODS FUSE is a hybrid, randomized, controlled trial/cohort study including participants of 17 prior EXU clinical trials. Pooled patient data from these trials were used, and the subset of patients enrolled in the follow-up cohort study was followed prospectively for 2 years in order to evaluate the incidence of fatal and nonfatal primary lung cancers and all-cause mortality. RESULTS A total of 24,409 person-years (PY) of observation among 7,439 trial patients, with 4,017 PY (16.5%) from the period after the trials but before the prospective follow-up and 5,299 PY (21.7%) from the prospective follow-up. Just over half of the 2,631 patients (51.6%) in the prospective follow-up were randomized to EXU in the original trial. The incidence density ratio was 2.8 (95% CI 0.5, 28.5) for lung cancer–related mortality and 3.7 (95% CI 1.0, 20.7) for incident primary lung cancer. The hazard ratio for all-cause mortality was 0.81 (95% CI 0.60, 1.10). CONCLUSIONS These data cannot exclude an increased risk of lung cancer–related mortality associated with EXU use. If real, the absolute increased risk of lung cancer–related mortality was small (0.48 cases per 1,000 PY). For all-cause mortality—the most reliably measured end point with the clearest interpretation—EXU users did not experience an excess all-cause death rate (relative nor absolute) compared with users of other diabetes treatments over the study period.