Objective: To evaluate the impact of baseline disease variables related to diabetes and diabetic neuropathy severity on efficacy and safety of duloxetine in the management of diabetic peripheral neuropathic pain.
Research design and methods: The impact of baseline conditions was evaluated using the data from three pooled placebo-controlled studies for combined duloxetine, doses of 60 mg q.d. and 60 mg b.i.d., versus placebo. The primary efficacy measure was the weekly mean of 24-h average pain severity, and night pain was the secondary measure. Safety and tolerability were assessed.
Results: There were no significant (P > 0.10) interactions of treatment by age (< 65 or > or = 65 years), type of diabetes (type 1 or type 2), duration of diabetes (median split < 9.18 or > or = 9.18 years), duration of diabetic neuropathy (< 2, 2 to < 6, or > or = 6 years), severity of diabetic neuropathy (baseline Michigan Neuropathy Screening Instrument score < 5 or > or = 5), baseline A1C level (median split < 7.6 or > or = 7.6%), or baseline insulin use (yes/no). Significant interactions for both pain measures were observed in baseline pain subgroups (Brief Pain Inventory average pain, > or = 6 and < 6). Duloxetine was more effective in the subgroup with more pain. No significant association was found between any other subgroups (P > 0.10). Significant interactions (P < 0.1) occurred with treatment-emergent adverse events when stratified by subgroups.
Conclusions: Pain severity but not variables related to diabetes or neuropathy may predict the effects of duloxetine in diabetic peripheral neuropathic pain. The efficacy of duloxetine is related to the initial pain severity and is generalizable across a broad spectrum of diabetic patients, including those with the highest severity of diabetes or neuropathy.
Trial registration: ClinicalTrials.gov NCT00058968.