title: Pancreatic safety in Japanese patients with type 2 diabetes treated with once weekly dulaglutide 0.75 mg up to 52 weeks in phase 3 clinical trials.
abstract: The effects of incretin therapies on pancreatic safety are currently being evaluated. In 3 phase 3 clinical studies of once weekly dulaglutide 0.75 mg (dulaglutide) in Japanese patients with type 2 diabetes (T2D), symptoms suggestive of acute pancreatitis as well as pancreatic enzymes were assessed and the risk of acute pancreatitis was evaluated. Patients who met any of the predefined criteria (clinical signs/symptoms of acute pancreatitis, confirmed amylase or lipase level ≥3 times the upper limit of normal [ULN], abdominal imaging of the pancreas) were adjudicated for acute pancreatitis by a blinded external committee. A total of 43 events in 40 patients (dulaglutide, 35/917 patients; liraglutide, 2/137 patients; insulin glargine, 2/180 patients; and placebo, 2/70 patients) were adjudicated (1 patient had events adjudicated during both placebo and dulaglutide treatment); 2 patients treated with dulaglutide had acute pancreatitis confirmed (2/917 [0.2%]; 2.651 patients/1,000 patient-years). One of these patients was diagnosed by the investigator with acute pancreatitis related to dulaglutide, but there was no typical abdominal pain. The event in the other patient occurred following an endoscopic ultrasound-guided fine needle aspiration. Transient increases in lipase ≥3×ULN were observed in 2% of patients in both the dulaglutide and liraglutide groups; the incidence in dulaglutide-treated patients was not significantly different from the incidences in liraglutide, placebo-, or insulin glargine-treated patients. Results of systematic assessments of pancreatic safety in 3 phase 3 studies for up to 52 weeks do not suggest an increased risk of acute pancreatitis in Japanese patients treated with dulaglutide.
authors.affiliation: Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Emoto
authors.forename: Tomonori
authors.initials: T
authors.lastname: Oura
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsui
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kazama
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Iwamoto
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D004763:Glucagon-Like Peptides; C555680:dulaglutide