A pooled analysis of exenatide use and risk of acute pancreatitis

Abstract

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.

Key words::

• Acute pancreatitis
• Antihyperglycemic agents
• Cohort study
• Exenatide BID
• Pharmacoepidemiology
• Relative risk correction
• Type 2 diabetes

Transparency

Declaration of funding

This study was funded by research contracts between OptumInsight and Amylin Pharmaceuticals Inc., and IMS Consulting and Amylin Pharmaceuticals Inc. Amylin Pharmaceuticals Inc. reviewed the study design, analytic output, and manuscript and provided non-binding comments to the authors. The contract granted OptumInsight oversight of the study conduct, reporting, and interpretation, as well as final wording of any resulting manuscripts.

Declaration of financial/other relationships

D.D.D., C.H., and J.D.S. were employees of OptumInsight and holders of stock and stock options in OptumInsights’s parent company, UnitedHealth Group at the time this work was conducted. M.H., E.M.P., and D.B.S. were employees of IMS Consulting.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

This work was presented in abstract form at the 2011 annual meeting of the International Society for Pharmacoepidemiology in Chicago, IL, USA.