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 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.
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.
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.
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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: email@example.com.