Association between incretin-based drugs and the risk of acute pancreatitis

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 Chowdhury Turin, Pierre Ernst, Samy Suissa, Brenda R. Hemmelgarn, Gary F. Teare, Patricia Caetano, Dan Chateau, David A. Henry, Jacques LeLorier & 3 others Adrian R. Levy, Ingrid S. Sketris, Canadian Network of Observational Drug Effect Studies (CNODES)

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

46 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1464-1473
Number of pages10
JournalJAMA Internal Medicine
Volume176
Issue number10
DOIs
Publication statusPublished - 1 Oct 2016
Externally publishedYes

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Incretins
Pancreatitis
Hypoglycemic Agents
Dipeptidyl-Peptidase IV Inhibitors
Pharmaceutical Preparations
Glucagon-Like Peptide 1
Type 2 Diabetes Mellitus
Population
Canada
Cohort Studies
Outcome Assessment (Health Care)
Incidence
Health

Cite this

Azoulay, L., Filion, K. B., Platt, R. W., Dahl, M., Dormuth, C. R., Clemens, K. K., ... Canadian Network of Observational Drug Effect Studies (CNODES) (2016). Association between incretin-based drugs and the risk of acute pancreatitis. JAMA Internal Medicine, 176(10), 1464-1473. https://doi.org/10.1001/jamainternmed.2016.1522
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 Chowdhury ; Ernst, Pierre ; Suissa, Samy ; Hemmelgarn, Brenda R. ; Teare, Gary F. ; Caetano, Patricia ; Chateau, Dan ; Henry, David A. ; LeLorier, Jacques ; Levy, Adrian R. ; Sketris, Ingrid S. ; Canadian Network of Observational Drug Effect Studies (CNODES). / Association between incretin-based drugs and the risk of acute pancreatitis. In: JAMA Internal Medicine. 2016 ; Vol. 176, No. 10. pp. 1464-1473.
@article{47d816274a3b42caa6d263c71ab6f4b2,
title = "Association between incretin-based drugs and the risk of acute pancreatitis",
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 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.",
author = "Laurent Azoulay and Filion, {Kristian B.} and Platt, {Robert W.} and Matthew Dahl and Dormuth, {Colin R.} and Clemens, {Kristin K.} and Madeleine Durand and Nianping Hu and Juurlink, {David N.} and Paterson, {J. Michael} and Targownik, {Laura E.} and Turin, {Tanvir Chowdhury} and Pierre Ernst and Samy Suissa and Hemmelgarn, {Brenda R.} and Teare, {Gary F.} and Patricia Caetano and Dan Chateau and Henry, {David A.} and Jacques LeLorier and Levy, {Adrian R.} and Sketris, {Ingrid S.} and {Canadian Network of Observational Drug Effect Studies (CNODES)}",
year = "2016",
month = "10",
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doi = "10.1001/jamainternmed.2016.1522",
language = "English",
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journal = "JAMA Internal Medicine",
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Azoulay, L, Filion, KB, Platt, RW, Dahl, M, Dormuth, CR, Clemens, KK, Durand, M, Hu, N, Juurlink, DN, Paterson, JM, Targownik, LE, Turin, TC, Ernst, P, Suissa, S, Hemmelgarn, BR, Teare, GF, Caetano, P, Chateau, D, Henry, DA, LeLorier, J, Levy, AR, Sketris, IS & Canadian Network of Observational Drug Effect Studies (CNODES) 2016, 'Association between incretin-based drugs and the risk of acute pancreatitis', JAMA Internal Medicine, vol. 176, no. 10, pp. 1464-1473. https://doi.org/10.1001/jamainternmed.2016.1522

Association between incretin-based drugs and the risk of acute pancreatitis. / 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 Chowdhury; Ernst, Pierre; Suissa, Samy; Hemmelgarn, Brenda R.; Teare, Gary F.; Caetano, Patricia; Chateau, Dan; Henry, David A.; LeLorier, Jacques; Levy, Adrian R.; Sketris, Ingrid S.; Canadian Network of Observational Drug Effect Studies (CNODES).

In: JAMA Internal Medicine, Vol. 176, No. 10, 01.10.2016, p. 1464-1473.

Research output: Contribution to journalArticleResearchpeer-review

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.

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DO - 10.1001/jamainternmed.2016.1522

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Azoulay L, Filion KB, Platt RW, Dahl M, Dormuth CR, Clemens KK et al. Association between incretin-based drugs and the risk of acute pancreatitis. JAMA Internal Medicine. 2016 Oct 1;176(10):1464-1473. https://doi.org/10.1001/jamainternmed.2016.1522