• Laurent Azoulay, Kristian B Filion, Robert W Platt, Matthew Dahl, Colin R Dormuth, Kristin K Clemens, Madeleine Durand, Nianping Hu, David N Juurlink, J Michael Paterson, Laura E Targownik, Tanvir C Turin, Pierre Ernst, and the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators, Samy Suissa, Brenda R Hemmelgarn, Gary F Teare, Patricia Caetano, Dan Chateau, David A Henry, Jacques LeLorier, Adrian R Levy, and Ingrid S Sketris.
• Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada2Department of Oncology, McGill University, Montreal, Quebec, Canada.
• JAMA Intern Med. 2016 Oct 1; 176 (10): 1464-1473.

ImportanceThe 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.ObjectiveTo 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 ParticipantsA 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.ExposuresCurrent use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs.Main Outcomes And MeasuresNested 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.ResultsOf 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 RelevanceIn 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.

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