OBJECTIVES: To compare the use of opioids and health care costs between patients with diabetic peripheral neuropathic pain (DPNP) who initiated treatment with duloxetine versus other standard of care DPNP treatments. METHODS: This retrospective cohort study analyzed administrative claims database 2004-2006 from a large US commercially-insured population to assess opioid utilization and healthcare costs over a one-year follow-up period. DPNP patients aged 18-64 years initiated on duloxetine (Dulox) or other standard of care (SOC) therapies, including tricyclic, venlafaxine, gabapentin, and pregabalin, between March 1, 2005 and December 31, 2005 were selected. Initiation of treatment was defined as no pill coverage over the prior 90 days. The first observed prescription claim denoted as the “index date”. SOC patients were randomly matched (ratio 1:1) to Dulox patients via propensity score matching controlling for patient demographics, clinical characteristics, and prior healthcare utilization. Opioid utilization and healthcare costs were compared between matched study cohorts. RESULTS: Propensity score matching resulted in 112 Dulox and 112 SOC patients. Compared with SOC patients, Dulox patients were less likely to use any DPNP-related opioids (52.7% vs. 82.1%, p<0.01). Patients who initiated duloxetine had 2.0 fewer opioids prescription dispensed (p<0.01) and 32 fewer days on opioids (p<0.01) than those in the SOC cohort. Patients in the Dulox cohort were initiated on opioids approximately four months later than SOC patients (p<0.01). The cumulative opioid dose in morphine equivalents were significantly lower for Dulox patients than SOC patients (833mg vs. 3,114mg, p<0.01). Dulox cohort had significantly lower total health care costs than SOC cohort ($22,273 vs. $34,785, p<0.05), primarily due to lower outpatient costs ($7,567 vs. $17,584, p<0.01). CONCLUSIONS: Duloxetine treatment appears to be associated with delayed use of opioids among patients with DPNP. Health care costs were also lower for patients initiated on duloxetine vs. SOC treatment.