BACKGROUND: Diabetes mellitus is associated with an increased risk of colorectal neoplasia and diabetes medications may further influence the risk. Observational studies of the effect of diabetes medications on colonic neoplasia may be biased if use of diabetes medications is associated with undergoing lower endoscopy. This study examined the association between diabetes therapies and use of lower endoscopy. METHODS: This retrospective cohort study included patients with diabetes in an integrated, prepaid health plan. The primary exposure variables were use of sulfonylureas, metformin, thiazolidinediones (TZDs), and insulin. The outcome measure was completion of a flexible sigmoidoscopy or colonoscopy. Cox proportional hazards modeling, accounting for the time-varying nature of the medication exposures, was used to generate estimates of the relative hazard (HR) of lower endoscopy with different medications. RESULTS: The study included 44 169 patients followed for a mean duration of 4.2 years (SD = 2.5 years); 34% underwent at least one lower endoscopy. Patients who filled a diabetes medication prescription were more likely to undergo lower endoscopy (HR = 1.13, 95%CI 1.06-1.21). Compared to those taking only sulfonylureas, patients receiving sulfonylureas and metformin (HR = 1.12, 95%CI 1.06-1.18) or metformin alone (HR = 1.17, 95%CI 1.07-1.26) were more likely to undergo lower endoscopy. For all medications, new use was associated with undergoing lower endoscopy (p < 0.05 for all comparisons). CONCLUSIONS: Diabetic patients receiving medications are more likely to undergo lower endoscopy than those on diet control alone, particularly in the first year after initiating a new medication class and if taking metformin.