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

Abstract

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.