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Incretin-based drugs and the incidence of colorectal cancer in patients with type 2 diabetes

Abrahami Devin; Yin, Hui; Yu, Oriana H Y; Pollak, Michael N; Azoulay, Laurent
doi: 10.1097/EDE.0000000000000793
Original Article: PDF Only


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.


Using data from the United Kingdom 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 one 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.


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 relationship for either drug.


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.

Conflicts of interest: There is no conflict of interest to declare.

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

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

Acknowledgments: Dr. Laurent Azoulay is the recipient of a Chercheur-Boursier career award from the Fonds de recherche du Québec – Santé and a William Dawson Scholar from McGill University.

Correspondence: Dr Laurent Azoulay, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital , 3755 Côte Sainte-Catherine, H-425.1, Montreal, Quebec, Canada, H3T 1E2, Tel: 514.340.8222 ext. 28396; Fax: 514.340.7564, Email:

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