A pooled analysis of exenatide use and risk of acute pancreatitis.

OBJECTIVE: To estimate the association between exenatide BID use and acute pancreatitis across two claims-based studies. RESEARCH DESIGN AND METHODS: We pooled two cohort studies within separate commercial health insurance databases. We included initiators of exenatide BID and all other antihyperglycemic drugs without prior pancreatitis from 2005-2008. Poisson regression models provided rate ratios (RRs) and 95% confidence intervals (CIs) of the association of exenatide BID with acute pancreatitis adjusted for quintiles of propensity scores. MAIN OUTCOME MEASURES: Primary inpatient diagnoses of acute pancreatitis with correction for misclassification via a validation sub-study. RESULTS: There were 49,956 initiators of exenatide BID and 692,333 initiators of other antihyperglycemic drugs. Patients in the two studies were similar on many demographic and clinical characteristics. Exenatide BID initiators had a higher prevalence of diagnoses consistent with diabetes complications (e.g. peripheral neuropathy) and cardiovascular risk factors (e.g. hypertension). In both studies, current exenatide BID use was not associated with uncorrected outcomes of acute pancreatitis (pooled RR 1.0; CI 0.8-1.3). PPV correction resulted in a slightly higher point estimate for current use (pooled RR 1.3; CI 1.0-1.7) and past use (pooled RR 1.6; 95% CI 1.2-2.1). CONCLUSIONS: These data are consistent with little or no higher risk of acute pancreatitis associated with current exenatide BID use relative to nonuse. Although previous work identified non-causal mechanisms, an increased incidence of acute pancreatitis following cessation of treatment remains a possibility. Bias due to residual confounding or outcome misclassification may remain, and should be considered a potential explanation for these findings.