OBJECTIVES: Opioids have commonly been used to treat chronic pain conditions, including diabetic peripheral neuropathic pain (DPNP), but tolerance issues have limited their use by providers. Newer classes of drugs are now approved for DPNP therapy, but no published data currently exists that assess changes in the utilization of opioid therapy following treatment with these newer agents. This study compared the use of opioids between DPNP patients who initiated treatment with duloxetine versus other standard of care (SOC) DPNP treatments. METHODS: This retrospective cohort study assessed commercially-insured DPNP patients aged 18 to 64 over a 1-year follow-up period who initiated treatment with either duloxetine or other SOC treatments (tricyclic, venlafaxine, gabapentin, pregabalin) between March 1,2005 and December 31, 2005. Initiation was defined as a 90-day period without available study medication. Dispense date of the first study medication initiation was denoted as the index date. Selected patients had 12 months continuous enrollment before and after the index date, and no opioid pill coverage during the 90 days prior to initiation. Patients were matched to duloxetine-treated patients via propensity scoring, controlling for demographics, comorbidities, prior health care utilization and costs, and medication history. RESULTS: The matched sample included 117 patients in each of the duloxetine and SOC cohorts. Compared with SOC patients, duloxetine-treated patients were less likely to use any opioids (52.1% vs. 84.6%, p<0.05) over the 12-month post-index period. Duloxetine-treated patients, on average, had 2 fewer opioid prescriptions dispensed, 27 fewer days on opioids, 120 days greater delay in subsequent opioid use, and 1816mg lower morphine equivalent dosage than SOC patients (all p<0.05). Also, duloxetine-treated patients had significantly lower total ($18,623 vs. $30,602, p<.05) and outpatient costs ($7,371 vs. $15,343, p<0.05). CONCLUSIONS: Duloxetine treatment is associated with deferred and reduced opioid use among DPNP patients. Patients initiated on duloxetine also had lower health care costs.