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Incretin-based Drugs and the Incidence of Colorectal Cancer in Patients with Type 2 Diabetes

Abrahami, Devina,b; Yin, Huia; Yu, Oriana H., Y.a,c; Pollak, Michael, N.d,e; Azoulay, Laurenta,d,f

doi: 10.1097/EDE.0000000000000793
Chronic diseases

Background: Evidence on the safety of the incretin-based drugs (glucagon-like peptide-1 [GLP-1] analogues and dipeptidyl peptidase-4 [DPP-4] inhibitors) with respect to colorectal cancer is contradictory. The objective of this study was to determine whether use of incretin-based drugs is associated with risk of incident colorectal cancer in patients with type 2 diabetes.

Methods: Using data from the UK Clinical Practice Research Datalink, we identified a cohort of 112,040 patients newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2015. We modeled use of GLP-1 analogues and DPP-4 inhibitors as time-varying variables and compared them with use of sulfonylureas. We lagged exposures by 1 year for latency and to reduce reverse causality and detection bias. We used time-dependent Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals of incident colorectal cancer associated with the use of GLP-1 analogues and DPP-4 inhibitors overall, by cumulative duration of use and by time since initiation.

Results: During 388,619 person-years of follow-up, there were 733 incident colorectal cancer events (incidence rate: 1.9 per 1,000 person-years). Use of GLP-1 analogues was not associated with colorectal cancer incidence (hazard ratio: 1.0; 95% confidence interval = 0.7, 1.6), nor was use of DPP-4 inhibitors (hazard ratio: 1.2; 95% confidence interval = 1.0, 1.5). There was no evidence of a duration–response relation for either drug.

Conclusions: The results of this large population-based study indicate that use of incretin-based drugs is not associated with colorectal cancer incidence among patients with type 2 diabetes.

From the aCentre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montréal, QC, Canada; bDivision of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC, Canada; cDivision of Endocrinology, Jewish General Hospital, Montreal, QC, Canada; dGerald Bronfman Department of Oncology, McGill University, Montréal, QC, Canada; eSegal Cancer Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada; and fDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada.

Submitted June 7, 2017; accepted July 15, 2017.

Availability of data and code: No additional data are available because it is not permitted according to agreements with the data custodians.

This study was funded by a Foundation Scheme Grant from the Canadian Institutes of Health Research.

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

Correspondence: Laurent Azoulay, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montreal, QC H3T 1E2, Canada. E-mail: laurent.azoulay@mcgill.ca.

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