Safety and tolerability of duloxetine in the acute management of diabetic peripheral neuropathic pain: analysis of pooled data from three placebo-controlled clinical trials.

OBJECTIVE

Summarize safety and tolerability of duloxetine in treating diabetic peripheral neuropathic pain.

RESEARCH DESIGN AND METHODS

Pooled data from three double-blind, randomized studies with 12-week, placebo-controlled (acute) and 52-week, routine-care-controlled (extension) phases.

MAIN OUTCOME MEASURES

Frequency/discontinuations due to treatment-emergent adverse events (TEAEs).

RESULTS

There were 1139 (placebo, n = 339; duloxetine, n = 800) and 867 (routine-care, n = 287; duloxetine, n = 580) patients in the acute and extension phases, respectively. Patient details were as follow: 60 years (mean age); Caucasian, 84%; and male, 57%. In the acute phase, there were significantly more TEAEs, duloxetine versus placebo (p = 0.001), the most common being nausea and somnolence. Discontinuations due to adverse events were significantly greater (12.5 vs 5.6%, p < 0.001), with similar outcomes in the extension phase. Baseline-to-endpoint aspartate transaminase/alanine transaminase were significantly increased and fasting plasma glucose was increased for duloxetine (0.67 mmol/l) versus decreased in routine-care (-0.64 mmol/l, p < 0.001). HbA1c was significantly increased, duloxetine vs routine-care, in the extension phase (52 vs 19%, p < 0.001). Endpoint measures neuropathy, nephropathy and retinopathy indicated no disease progression.

CONCLUSIONS

Duloxetine was generally safe and well tolerated, with the three most commonly reported TEAEs being nausea, somnolence and constipation. Modest changes in glycemia were associated with duloxetine. Aspartate transaminase/alanine transaminase increases were transient and not considered predictive of more severe outcomes.