Table 2.

Studies examining GLP-1 RA therapy and risk of pancreatitis in patients with T2DM.

Study Model	Study Methods	Pancreatic Outcomes	Study Critique
Human Tissue
Butler 2013 [61]	Pancreata from organ donors • 1 exenatide treated, 7 sitagliptin treated vs other therapy	• Enlargement of exocrine and endocrine pancreatic compartments • Exocrine cell proliferation • α-cell hyperplasia	• Uncontrolled differences between comparison groups confound interpretation of study findings
Human Databases
Dore 2009 [62]	Large US healthcare claims database • Claims for hospitalizations with primary diagnosis of pancreatitis • Comparison of users of exenatide or sitagliptin therapy with users of metformin or glyburide	• No increased risk of pancreatitis	• Methodological flaws associated with claims databases
Dore 2011 [63]	Large US healthcare claims database • Comparison of users of exenatide vs comparators • Rate of pancreatitis confirmed through review of blinded medical records	• No increased risk of pancreatitis with current, recent or past exenatide use	• Methodological flaws associated with claims databases
Elashoff 2011 [64]	FDA AERS database • Comparison of users of exenatide or sitagliptin therapy with users of rosiglitazone, nateglinide, repaglinide, and glipizide	• Increased OR for reported pancreatitis among users of exenatide or sitagliptin	• Significant sources of bias, such as the notoriety bias, associated with the AERS database
Garg 2010 [65]	Large US healthcare claims database • Comparison of exenatide or sitagliptin use with nondiabetic control group and diabetic control group	• Greater risk of pancreatitis in diabetic groups compared with nondiabetic group • Similar risk of pancreatitis between exenatide group and diabetes comparator group	• Methodological flaws associated with claims databases
Romley 2012 [66]	Privately insured US patients • Exenatide use vs other treatment	• No association between exenatide use and hospitalization for acute pancreatitis	• Methodological flaws associated with claims databases
Singh 2013 [67]	Large US healthcare claims database • Comparison of hospitalized acute pancreatitis cases with matched controls	• Increased OR of acute pancreatitis with current or recent use of exenatide or sitagliptin	• Methodological flaws associated with claims databases
Wenten 2012 [68]	Large US healthcare claims database • Current, recent, past use exenatide	• No increased risk pancreatitis	• Methodological flaws associated with claims databases
Human Clinical Trial Meta-Analysis
Alves 2012 [69]	25 clinical studies involving exenatide or liraglutide therapy vs comparators	• No increased risk of pancreatitis	• Included studies did not have pancreatitis as a predefined primary outcome with predefined diagnostic criteria