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Original Investigation
October 2016

Association Between Incretin-Based Drugs and the Risk of Acute Pancreatitis

Author Affiliations
  • 1Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada
  • 2Department of Oncology, McGill University, Montreal, Quebec, Canada
  • 3Department of Medicine, McGill University, Montreal, Quebec, Canada
  • 4Departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
  • 5The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
  • 6Manitoba Centre for Health Policy, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  • 7Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada
  • 8Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
  • 9Department of Medicine, Western University, London, Ontario, Canada
  • 10Department of Internal Medicine, University of Montreal Health Centre, Montreal, Quebec, Canada
  • 11Health Quality Council, Saskatoon, Saskatchewan, Canada
  • 12Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
  • 13Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Toronto
  • 14Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada
JAMA Intern Med. 2016;176(10):1464-1473. doi:10.1001/jamainternmed.2016.1522

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.