Association Between Incretin-Based Drugs and the Risk of Acute Pancreatitis Academic Article uri icon

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abstract

  • Importance: The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial. Objective: To determine whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis. Design, Setting, and Participants: A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom. An overall cohort of 1 532 513 patients with type 2 diabetes initiating the use of antidiabetic drugs between January 1, 2007, and June 30, 2013, was included, with follow-up until June 30, 2014. Exposures: Current use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs. Main Outcomes and Measures: Nested case-control analyses were conducted including hospitalized patients with acute pancreatitis matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and follow-up duration. Hazard ratios (HRs) and 95% CIs for hospitalized acute pancreatitis were estimated and compared current use of incretin-based drugs with current use of 2 or more oral antidiabetic drugs. Secondary analyses were performed to assess whether the risk varied by class of drug (DPP-4 inhibitors and GLP-1 agonists) or by duration of use. Site-specific HRs were pooled using random-effects models. Results: Of 1 532 513 patients included in the analysis, 781 567 (51.0%) were male; mean age was 56.6 years. During 3 464 659 person-years of follow-up, 5165 patients were hospitalized for acute pancreatitis (incidence rate, 1.49 per 1000 person-years). Compared with current use of 2 or more oral antidiabetic drugs, current use of incretin-based drugs was not associated with an increased risk of acute pancreatitis (pooled adjusted HR, 1.03; 95% CI, 0.87-1.22). Similarly, the risk did not vary by drug class (DPP-4 inhibitors: pooled adjusted HR, 1.09; 95% CI, 0.86-1.22; GLP-1 agonists: pooled adjusted HR, 1.04; 95% CI, 0.81-1.35) and there was no evidence of a duration-response association. Conclusions and Relevance: In this large population-based study, use of incretin-based drugs was not associated with an increased risk of acute pancreatitis compared with other oral antidiabetic drugs.

authors

  • Azoulay, Laurent
  • Filion, Kristian B
  • Platt, Robert W
  • Dahl, Matthew
  • Dormuth, Colin R
  • Clemens, Kristin K
  • Durand, Madeleine
  • Hu, Nianping
  • Juurlink, David N
  • Paterson, J Michael
  • Targownik, Laura E
  • Turin, Tanvir C
  • Ernst, Pierre
  • Suissa, Samy
  • Dormuth, Colin R
  • Hemmelgarn, Brenda R
  • Teare, Gary F
  • Caetano, Patricia
  • Chateau, Dan
  • Henry, David A
  • Paterson, J Michael
  • LeLorier, Jacques
  • Levy, Adrian R
  • Ernst, Pierre
  • Platt, Robert W
  • Sketris, Ingrid S

publication date

  • October 1, 2016

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