OBJECTIVES:  Patients whose diabetes is managed with polypharmacy are subject to increased risk of medication-related problems and non-adherence. The objective of this drug therapy management (DTM) program is to integrate pharmacy intervention with care management to improve health and reduce cost. METHODS: The DTM program is a collaboration between pharmacy benefits management (PerformRx) and health plan-based care management (Keystone Mercy Health Plan [KMHP] and AmeriHealth Mercy Health Plan [AMHP]) targeting members with diabetes who are high utilizers (≥15 medications). Pharmacists review member profiles to recommend evidence-based prescriber and/or member interventions (e.g., changes in therapy, medication reminders) Pharmacists work directly with prescribers to optimize drug therapy, while care management provides detailed member coaching to enhance medication adherence. The profiles of 954 DTM participants (690 KMHP; 264 AMHP)—with a mean seven-fold greater disease burden than the plan average (using DxCG prospective risk scoring)—were reviewed for services between November 1, 2010 to July, 1, 2011, followed by a 3-month claims run-out period, while profiles of 810 matched control participants (600 KMHP; 210 AMHP) were not reviewed. RESULTS: Inpatient (IP) admissions and emergency room (ER) utilization rates were lower in the DTM population; however, only the DTM group in KMHP demonstrated a statistically significant reduction in IP admissions compared to the control group (76.4%; p=0.0002). Additionally, although pharmacy-related costs were significantly increased across-the-board, the changes were not statistically significant between DTM and control groups; however, total costs (medical+pharmacy) were significantly reduced in the DTM group compared to the control group (47.8% for KMHP, p=0.0039; 50.7% for AMHP, p=0.0497). The overall acceptance rates for diabetes-specific DTM interventions for KMHP and AMHP members were 33% and 26%, respectively. CONCLUSIONS: DTM Participants demonstrated a significant total cost savings in both health plans, and modest-to-significant reductions in ER visits and IP admission compared to non-participants.