TY - JOUR
T1 - Association between incretin-based drugs and the risk of acute pancreatitis
AU - Azoulay, Laurent
AU - Filion, Kristian B.
AU - Platt, Robert W.
AU - Dahl, Matthew
AU - Dormuth, Colin R.
AU - Clemens, Kristin K.
AU - Durand, Madeleine
AU - Hu, Nianping
AU - Juurlink, David N.
AU - Paterson, J. Michael
AU - Targownik, Laura E.
AU - Turin, Tanvir Chowdhury
AU - Ernst, Pierre
AU - Suissa, Samy
AU - Hemmelgarn, Brenda R.
AU - Teare, Gary F.
AU - Caetano, Patricia
AU - Chateau, Dan
AU - Henry, David A.
AU - LeLorier, Jacques
AU - Levy, Adrian R.
AU - Sketris, Ingrid S.
AU - Canadian Network of Observational Drug Effect Studies (CNODES)
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 analyseswere 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.
AB - 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 analyseswere 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.
UR - http://www.scopus.com/inward/record.url?scp=84997521885&partnerID=8YFLogxK
U2 - 10.1001/jamainternmed.2016.1522
DO - 10.1001/jamainternmed.2016.1522
M3 - Article
C2 - MEDLINE:27479930
AN - SCOPUS:84997521885
SN - 2168-6106
VL - 176
SP - 1464
EP - 1473
JO - JAMA Internal Medicine
JF - JAMA Internal Medicine
IS - 10
ER -
