SAN DIEGO—A 1-year study of approximately 200 patients suggests that duloxetine (Cymbalta) is as safe and well tolerated as routine care for diabetic peripheral neuropathic pain (DPNP). The results, which were presented at the 22nd Annual Meeting of the American Academy of Pain Medicine, also suggest that this agent had no deleterious effects on the progression of diabetes or many of the associated complications, including damage to the nerves, kidneys, or eyes.
This trial included outpatients aged Ž18 years who had been diagnosed with moderate-to-severe DPNP caused by type 1 or type 2 diabetes. Patients who completed 13 weeks of randomized, double-blind, placebo-controlled acute therapy were randomly reassigned to duloxetine 60 mg twice daily (n = 197) or to routine care (n = 96) for an additional 52 weeks.
Routine care consisted primarily of thioctic acid, cyanocobalamin/benfotiamine, paracetamol, amitriptyline, and benfotiamine. No significant differences were reported between the 2 groups in overall incidence of adverse events resulting from treatment or quality-of-life measures.
“This study was designed to give us some long-term data. You always wonder after just a 12-week study what the safety is long-term, so we wanted to investigate that,” coinvestigator Tim Smith, MD, of Washington University School of Medicine, St. Louis, Mo, told IMWR. “Many physicians are now doing things off-label, and there have been problems with side effects with various agents. Some agents were not ?effective, such as gabapentin [Neurontin]. So there were no controlled studies. Now we have data showing that duloxetine is safe and effective for up to 1 year.”
Overall, 14 patients (4.8%) discontinued therapy due to adverse events or death (3 in the routine care group and 11 in the duloxetine group). Treatment-emergent adverse events reported by Ž5% of the duloxetine-treated patients were fatigue, hyperhidrosis, nausea, and asthenia; Ž5% of the routine care patients reported nasopharyngitis.
Peripheral neuropathy affects up to 50% of patients with diabetes in the United States.
Diabetic neuropathy is difficult to treat because of drug side effects and the development of tolerance.
Duloxetine improved the pain associated with diabetic neuropathy and was safe and effective in this patient population for up to 1 year.
This drug had no adverse effects on diabetes progression or its associated complications.
Duloxetine did not appear to adversely affect glycemic control, lipid profiles, or nerve or eye function. There were no significant between-group differences in mean change in systolic blood pressure (BP), weight, or electrocardiographic parameters. Duloxetine-treated patients experienced a slight but significant increase in sitting diastolic BP and pulse compared with the routine care patients; the latter had a slight decrease in mean pulse rate.
“The blood pressure differences were statistically significant but of doubtful clinical relevance,” Dr Smith said, adding that the data require corroboration in future studies.
There were significant differences between the 2 groups that favor?ed the duloxetine group in Medical Outcomes Study Short Form-36 physical component scores and ?subscale scores of physical functioning, bodily pain, mental health, and overall vitality.
Although the mechanism of action of duloxetine in humans is not fully understood, its effects on pain perception may be due to increased serotonin and norepinephrine activity in the central nervous system.
“This is important information that demonstrates that duloxetine is safe and effective for up to 1 year in the treatment of DPNP. Of particular note is that the treatment with duloxetine did not significantly affect glycemic control, weight, or blood pressure over the year of study. This might provide reassurance to physicians that duloxetine does not appear to adversely affect the course of diabetes,” said Lesley Arnold, MD, of the University of Cincinnati in Ohio.