Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors

Aims: Incretin-based antihyperglycemic therapies increase intestinal mucosal expansion and polyp growth in mouse models. We aimed to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1ra) initiation on colorectal cancer incidence.

Methods: We conducted a cohort study on US Medicare beneficiaries over age 66 from 2007 to 2013 without prevalent cancer. We identified three active-comparator and new-user cohorts: DPP-4i versus thiazolidinediones (TZD), DPP-4i versus sulphonylureas (SU), and GLP-1ra versus long acting insulin (LAI). Follow-up started from 6 months post-second prescription and ended 6 months after stopping (primary as-treated analysis). We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for incident colorectal cancer adjusting for measured confounders using propensity score weighting.

Results: The median duration of treatment ranged 0.7-0.9 years among DPP-4i cohorts. Based on 104 events among 39,334 DPP-4i and 63 events among 25,786 TZD initiators, there was no association between DPP-4i initiation and colorectal cancer (adjusted HR = 1.17 (CI 0.88, 1.71)). There were 73 events among 27,047 DPP-4i and 266 events among 76,012 SU initiators with the adjusted HR 0.98 (CI 0.74, 1.30). We identified 5600 GLP-1ra and 54,767 LAI initiators and the median duration of treatment was 0.8 and 1.2 years, respectively. The adjusted HR was 0.82 (CI 0.42, 1.58) based on <11 events among GLP-1ra versus 276 events among LAI initiators.

Conclusion: Although limited by the short duration of treatment, our analyses based on real-world drug utilization patterns provide evidence of no short-term effect of incretin-based agents on colorectal cancer.