Pioglitazone Exposure Reduced the Risk of All-Cause Mortality in Insulin-Treated Patients with Type 2 Diabetes Mellitus

Context: The long-term safety and benefit of pioglitazone use in combination with insulin are still uncertain. Objective: This study compared the risks of all-cause mortality and major cardiovascular (CV) events between pioglitazone users and nonusers receiving insulin therapy. Design, Setting and Patients: We conducted a 13-year retrospective cohort study by using data from the population-based National Health Insurance Research Database in Taiwan. A total of 20 376 patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy were enrolled during 2000 to 2012. Overall, the incidence rates of all-cause mortality and CV events were compared between 2579 pioglitazone users and 2579 matched nonusers. Results: After adjustment for age, sex, comorbidities, Diabetes Complications Severity Index scores, and drugs used, mortality rates were 30.26 and 15.02 per 1000 person-years for pioglitazone nonusers and users, respectively. The adjusted hazard ratio (aHR) of mortality was 0.47 (95% confidence interval [CI]: 0.38-0.58, P < 0.001) for pioglitazone users compared with nonusers. The aHRs of CV and non-CV deaths were 0.78 (95% CI: 0.51-1.19) and 0.50 (95% CI: 0.38-0.66), respectively. The aHRs of hospitalized coronary artery disease, hospitalized stroke, and incident heart failure were not significantly different between pioglitazone users and nonusers. Conclusions: This nationwide cohort study demonstrated that pioglitazone use reduced the risks of all-cause mortality and non-CV death for patients with T2DM undergoing insulin therapy.