OBJECTIVES: To compare diabetes-related complications, utilizations and costs between diabetes patients treated with DPP4i-based combinations (DPP4i+MET or DPP4i+PIO) vs. SU-based combinations (SU+MET or SU+PIO).  METHODS: MarketScan, a U.S. database of insured members, was analyzed to retrospectively compare outcomes between patients treated with DPP4i and SU combinations.  The study sample consisted of T2DM patients who received DPP4i or SU combinations and had continuous eligibility from 6 months prior to and 12 months following the index date (date of combination therapy initiation).  Rates of diabetic complications, healthcare utilization, and costs in 12-month follow-up period were assessed.  Complications included microvascular (e.g. diabetic retinopathy), macrovascular (e.g. atherosclerosis), and other diabetic complications.  Cox proportional hazards models were used to compare complication rates, adjusting for baseline characteristics.  Generalized linear models/two-part models were similarly used for utilizations and costs. RESULTS: The study included 15,139 patients (47.0% female; mean age 52.6 [SD=8.1]) receiving DPP4i combinations and 41,602 patients (42.4% female; mean age 51.9 [SD=8.3]) receiving SU combinations.  At baseline, DPP4i patients had higher rates of medication use than SU patients (MET: 61.7% vs. 40.4%; TZD: 23.0% vs. 11.8%; lipid-lowering: 53.2% vs. 35.4%; number of different medications: 7.2 [SD=5.1] vs. 5.3 [SD=4.9], respectively; all P<0.0001).  After adjustment, hazard ratios of complications were significantly lower for patients treated with DPP4i combinations (microvascular complications: 0.872, P<0.0001; macrovascular complications: 0.933, P=0.0015; other complications: 0.921, P<0.0001).  DPP4i patients also had lower adjusted diabetes-related utilization incidence rate ratios (hospitalization: 0.76; ER visits: 0.69; outpatient visits: 0.87; all P<0.0001).  DPP4i patients incurred higher mean diabetes-related prescription drug costs ($1,629 vs. $476, P<0.0001) but lower all-cause medical services costs ($6731 vs. $7251, P<0.0001). CONCLUSIONS: Compared to SU combinations, DPP4i combinations are associated with lower rates of diabetic complications and health care utilization.  While patients on DPP4i combination incur higher diabetes-related drug costs, they were found to have lower all-cause medical-services costs.