Laurent Azoulay1, Kristian B Filion2, Robert W Platt3, Matthew Dahl4, Colin R Dormuth5, Kristin K Clemens6, Madeleine Durand7, Nianping Hu8, David N Juurlink9, J Michael Paterson10, Laura E Targownik11, Tanvir C Turin12, Pierre Ernst2, Samy Suissa, Colin R Dormuth5, Brenda R Hemmelgarn, Gary F Teare, Patricia Caetano, Dan Chateau, David A Henry, J Michael Paterson10, Jacques LeLorier, Adrian R Levy, Pierre Ernst2, Robert W Platt3, Ingrid S Sketris. 1. Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada2Department of Oncology, McGill University, Montreal, Quebec, Canada. 2. Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada3Department of Medicine, McGill University, Montreal, Quebec, Canada. 3. Departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada5The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. 4. Manitoba Centre for Health Policy, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada7Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada. 5. Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. 6. Department of Medicine, Western University, London, Ontario, Canada. 7. Department of Internal Medicine, University of Montreal Health Centre, Montreal, Quebec, Canada. 8. Health Quality Council, Saskatoon, Saskatchewan, Canada. 9. Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. 10. Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada13Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Toronto. 11. Manitoba Centre for Health Policy, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada13Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Toronto. 12. Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada.
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.
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: Stacey A Seggelke; Mark C Lindsay; Ingrid Hazlett; Rebecca Sanagorski; Robert H Eckel; Cecilia C Low Wang Journal: Curr Diab Rep Date: 2017-08 Impact factor: 4.810