title: Pancreatic Safety of Sitagliptin in the TECOS Study.
abstract: We evaluated the incidence of acute pancreatitis and pancreatic cancer in patients with type 2 diabetes and cardiovascular disease who were treated with sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i).
  
  
  
  In the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study, a cardiovascular safety study of sitagliptin, all suspected cases of acute pancreatitis and pancreatic cancer were collected prospectively for 14,671 participants during a median follow-up time of 3 years, and were adjudicated blindly.
  
  
  
  Baseline differences were minimal between participants confirmed to have no pancreatic events, acute pancreatitis, or pancreatic cancer. Among those participants randomized to receive sitagliptin, 23 (0.3%) (vs. 12 randomized to receive placebo [0.2%]) had pancreatitis (hazard ratio 1.93 [95% CI 0.96-3.88], P = 0.065; 0.107 vs. 0.056/100 patient-years), with 25 versus 17 events, respectively. Severe pancreatitis (two fatal) occurred in four individuals allocated to receive sitagliptin. Cases of pancreatic cancer were numerically fewer with sitagliptin (9 [0.1%]) versus placebo (14 [0.2%]) (hazard ratio 0.66 [95% CI 0.28-1.51], P = 0.32; 0.042 vs. 0.066 events/100 patient-years). Meta-analysis with two other DPP-4i cardiovascular outcome studies showed an increased risk for acute pancreatitis (risk ratio 1.78 [95% CI 1.13-2.81], P = 0.01) and no significant effect for pancreatic cancer (risk ratio 0.54 [95% CI 0.28-1.04], P = 0.07).
  
  
  
  Pancreatitis and pancreatic cancer were uncommon events with rates that were not statistically significantly different between the sitagliptin and placebo groups, although numerically more sitagliptin participants developed pancreatitis and fewer developed pancreatic cancer. Meta-analysis suggests a small absolute increased risk for pancreatitis with DPP-4i therapy.
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC jbuse@med.unc.edu.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
authors.forename: M Angelyn
authors.initials: MA
authors.lastname: Bethel
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Green
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Pontificia Universidad Javeriana, Hospital Universitario San Ignacio, Bogotá, Colombia.
authors.forename: Pablo
authors.initials: P
authors.lastname: Aschner
authors.affiliation: Centre Region CINVEC, Viña del Mar, Chile.
authors.forename: Carlos Raffo
authors.initials: CR
authors.lastname: Grado
authors.affiliation: University Specialized Hospital for Active Treatment in Endocrinology, Medical University, Sofia, Bulgaria.
authors.forename: Tsvetalina
authors.initials: T
authors.lastname: Tankova
authors.affiliation: E. Wolfson Medical Center, Holon, Israel.
authors.forename: Julio
authors.initials: J
authors.lastname: Wainstein
authors.affiliation: St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Josse
authors.affiliation: The George Washington University Biostatistics Center, Rockville, MD.
authors.forename: John M
authors.initials: JM
authors.lastname: Lachin
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Engel
authors.affiliation: Toronto Centre for Liver Disease, Division of Gastroenterology, University of Toronto Health Network, Toronto, Ontario, Canada.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.affiliation: Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
authors.forename: Rury R
authors.initials: RR
authors.lastname: Holman
mesh_terms: D000208:Acute Disease; D000368:Aged; D002318:Cardiovascular Diseases / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000175:diagnosis*; D010195:Pancreatitis / Q000139:chemically induced / Q000175:diagnosis*; D016016:Proportional Hazards Models; D012307:Risk Factors; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000068900:Sitagliptin Phosphate