Thiazolidinedione use and risk of hospitalization for pneumonia in type 2 diabetes: population based matched case-control study [version 1; referees: 2 approved with reservations]

Objective: Previous randomized clinical trials and their meta-analyses have raised the possibility that thiazolidinediones (rosiglitazone and pioglitazone) may increase the risk of pneumonia. We aimed to test the hypothesis that thiazolidinediones may increase the risk of pneumonia. Design: Population based case-control study using a new user design. Setting: A large administrative database in the United States from 2002 to 2008. Population: Adults with type 2 diabetes aged 18-64; restricted to 6129 hospitalized pneumonia cases and 6129 controls without congestive heart failure matched on age, sex, enrollment pattern and diabetes complication severity index matched controls. Conditional logistic regression was used to analyse the data. Results: Compared with controls, cases were more likely to have chronic obstructive pulmonary disease (COPD), tobacco use, cancer and have received influenza and pneumococcal vaccination. After adjusting for COPD, cancer, tobacco use, and receipt of influenza and pneumococcal vaccination, and exposure in other periods, neither recent exposure to pioglitazone (adjusted Odds Ratio [aOR], 1.15, 95% Confidence intervals 1.00 – 1.32) or rosiglitazone (aOR 1.09, 95% CI, 0.83 – 1.44) nor current exposure to pioglitazone within 60 days (aOR, 1.04, 95% CI, 0.60 – 1.79) was associated with a statistically significant odds of pneumonia. Current exposure to rosiglitazone was associated with a statistically significant reduction in the odds of pneumonia (aOR, 0.33, 95% CI 0.11-0.95). Conclusion: In this study of US adults with type 2 diabetes we did not detect a significant increased risk of pneumonia with the thiazolidinediones. The unusually large protective effect of current exposure to rosiglitazone reflects the healthy user effect or unmeasured confounding.