Background: DPP44 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1Ra) control type 2 diabetes (T2DM) by promoting GLP-1 pathway; its activation can lead to dysplasia or tumor inhibition based on tissue types. Moreover, DPP4 can act as a tumor suppressor or activator. Few studies have looked at the risk of DPP4i and GLP1Ra on various types of cancer. Methods: We inquired an aggregated electronic health record database, Explorys (IBM, NY). Patients (Pts) diagnosed with T2DM from 1/05 to 6/19 were included and followed for 5 years after starting DPP4i, GLP1Ra, or metformin. Odds ratio (OR) were calculated after 6mo of lag time. Results: We identified 344,550, 112,000, and 1,245,930 pts in the DPP4i, GLP1Ra, and metformin group, respectively. The three groups were well balanced except pts in the GLP1Ra group had higher BMI. Within 5 years, 24,260 pts (9.5%) in DPP4i, 5,580 (8.7%) in GLP1Ra, and 57,490 (9.3%) in metformin group developed any types of cancer. When adjusted for sex, age, smoking status, alcohol abuse history, hemoglobin A1C (≤9.0% vs > 9.0%) and BMI ( < 30 vs ≥30 kg/m²) around initiation of antidiabetic agents, the aOR was 1.01 (95%CI .94-1.08) for DPP4i and 1.06 (95%CI .93-1.20) for GLP1Ra, comparing with the metformin group. For specific cancer types, DPP4i users were associated with significantly higher risk of bladder, kidney, liver cancer and melanoma; while the risk of breast, lung and prostate cancer were reduced. GLP1Ra users were associated with higher risk of thyroid cancer; while the risk of bladder, colon, lung, and prostate cancer were reduced. Conclusions: DPP4i and GLP1Ra were not associated with increased cancer risk overall. However, they were associated with increased or decreased risk of specific cancer types.