title: Incretin-based therapy and acute cholecystitis: a review of case reports and EudraVigilance spontaneous adverse drug reaction reporting database.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) receptor agonists delay gastric and bowel emptying. A similar inhibitory effect of GLP-1 on gallbladder motility has been suggested, possibly leading to an increased risk of cholecystitis related to incretin-based medications, which include GLP-1 antagonists. Our objective was to review evidence in EudraVigilance, the European spontaneous reporting database and the scientific literature on this issue.
  
  
  CONCLUSIONS
  Increasing evidence suggests an association of incretins with gallbladder adverse events. Pharmacovigilance data from EudraVigilance includes 200 serious ADR reports concerning cholecystitis related to the use of incretin-based therapies. Several mechanisms may explain this increased risk of cholecystitis, including rapid weight loss, inhibition of gallbladder contraction and emptying, reduced bile acids production, modulation of inflammation.
  
  
  CONCLUSIONS
  The available data suggest the possibility of gallbladder disease in diabetic subjects treated with incretins and highlight the importance of evaluating risk factors for cholelithiasis and gallbladder diseases in patients with diabetes before starting this therapy.
authors.affiliation: Department of Clinical Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Pizzimenti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giandalia
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cucinotta
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: G T
authors.initials: GT
authors.lastname: Russo
authors.affiliation: Department of Internal Medicine, Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Smits
authors.affiliation: Sicilian Regional Centre of Pharmacovigilance, Clinical Pharmacology Unit -AOU Policlinico "G. Martino", Messina, Italy.
authors.forename: P M
authors.initials: PM
authors.lastname: Cutroneo
authors.affiliation: Department of Clinical Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Trifirò
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D041881:Cholecystitis, Acute / Q000139:chemically induced*; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology*; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D054795:Incretins / Q000009:adverse effects*
chemical_list: D054795:Incretins; D052216:Glucagon-Like Peptide 1
keywords: gallbladder diseases; incretin-based therapy; type 2 diabetes mellitus