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

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 for Observational Drug Effect Studies (CNODES) Investigators. JAMA Intern Med. 2016; 315(20):2211-20. Epub 2016 May 24.


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.

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Keywords: Risk assessment Diabetes Drug therapy

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