title: Pancreatitis associated with the use of GLP-1 analogs and DPP-4 inhibitors: a case/non-case study from the French Pharmacovigilance Database.
abstract: In the recent past, concerns have raised regarding the potential risk of acute pancreatitis among type 2 diabetic patients using incretin-based drugs such as glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors. The aim of this study is to investigate the association between exposure to incretin-based drugs and the occurrence of pancreatitis reported in the French Pharmacovigilance Database. The case/non-case method was performed from serious adverse drug reactions (ADRs) involving antihyperglycemic agents (except insulin alone) reported to the French pharmacovigilance system between March 2008 (first marketing of an incretin-based drug in France) and March 2013. Cases were defined as reports of pancreatitis, and all other serious ADRs were considered non-cases. Disproportionality was assessed by calculating reporting odds ratios (ROR) adjusted for age, gender, history of pancreatitis, other antihyperglycemic drugs and other drugs associated with a higher risk of pancreatitis. Among 3,109 serious ADRs, 147 (4.7 %) reports of pancreatitis were identified as cases and 2,962 reports (95.3 %) of other ADRs as non-cases. Among the cases, 122 (83.0 %) involved incretin-based drugs. Disproportionality was found for all incretin-based drugs (adjusted ROR: 15.7 [95 % CI 9.8-24.9]), all GLP-1 analogs (29.4 [16.0-53.8]), exenatide (28.3 [12.8-62.3]), liraglutide (30.4 [15.4-60.0]), all DPP-4 inhibitors (12.1 [7.3-20.0]), sitagliptin (12.4 [7.3-21.0]), saxagliptin (15.1 [4.3-52.7]), and vildagliptin (7.4 [3.1-17.6]). Temporal analysis found disproportionality for incretin-based drugs since their first year of marketing in France. Compared with other antihyperglycemic agents, use of incretin-based drugs is associated with an increased risk of reported pancreatitis in France.
authors.affiliation: Department of Medical Pharmacology and Toxicology, Pharmacovigilance Regional Center, CHRU Montpellier, 371 Avenue du Doyen Gaston Giraud, 34295, Montpellier, France, jl-faillie@chu-montpellier.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Faillie
authors.forename: Samy
authors.initials: S
authors.lastname: Babai
authors.forename: Sabrina
authors.initials: S
authors.lastname: Crépin
authors.forename: Virginie
authors.initials: V
authors.lastname: Bres
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Laroche
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Louet
authors.forename: Pierre
authors.initials: P
authors.lastname: Petit
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
authors.forename: Dominique
authors.initials: D
authors.lastname: Hillaire-Buys
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005602:France / Q000453:epidemiology; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000453:epidemiology / Q000209:etiology*; D060735:Pharmacovigilance
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1