In a pooled analysis of 1,510 patients enrolled in seven randomized controlled trials, pregabalin (150–600 mg/day) provided significant improvements in pain, sleep interference due to pain, and global health, said Roy Freeman, MD, Harvard Medical School, Boston, Massachusetts, United States. Improvements in pain were dose-related; a clinically meaningful (≥30%) improvement in pain was noted by 43- 62%, though 37% of placebo patients also reported this level of improvement.

“There was a dose-related rapid onset of durable pain relief,” Dr. Freeman reported. While pregabalin was well tolerated overall, there was also a dose-related increase in weight gain of approximately 2 kg. For 4% of the 600 mg group, the weight gain was a clinically meaningful increase of at least 7% of body weight. Peripheral edema occurred in 10% (300 mg) to 16% (600 mg). “Clearly the 600 mg dose was more effective, though there were more side-effects,” Dr. Freeman said.

Results of another international study, the NATHAN 1 Study, showed that antioxidant treatment with α-lipoic acid improved some neuropathic deficits and symptoms in mild to moderate diabetic neuropathy, but did not affect nerve conduction, based on a composite neurological assessment. The randomized study included 454 subjects given α-lipoic acid 600 mg/day. After 4 years of treatment, the difference between the treatments based on the changes of the composite score including clinical signs (neuropathic deficits) and nerve conduction was only 0.7 points, but the neuropathic deficits did improve in the α-lipoic acid-treated group compared to placebo administration. Dan Ziegler, MD, German Diabetes Center, Dusseldorf, Germany, noted that the “marginal progression” of neuropathy in the placebo arm made it difficult to show a treatment effect. “The designs of future trials must assume a long-term stable neuropathic condition,” he said.

Perspective

MD Conference Express asked Nicolaas C. Schaper, MD, PhD, Professor of Endocrinology and Diabetes at University Hospital, Maastricht, the Netherlands, and session moderator, to comment on the studies reported at the Novel Therapies for Peripheral Neuropathy session.

He first noted that there are problems with clinical trials of agents. “You see a huge placebo effect in many studies, as in this study with pregabalin, and many are too short to be clinically relevant,” he pointed out. Another problem is the inconsistency between epidemiologic data and clinical trial data, he said. Epidemiologic data suggest there is a steady deterioration in nerve function over time however, a study reported at this EASD showed very little deterioration among trial subjects. “Clinical trials, therefore, may not reflect our clinical practice with this complication,” he said.

In studies reported at the EASD α-lipoic acid and aldose reductase inhibitors were found to be either problematic or with relative small effects. “While there may be short-term efficacy in reducing pain with pregablin, there were some relevant side-effects, including edema and weight gain. If these appear by 13 weeks, as shown in this study, then what happens after treatment for 10 years? We need to think carefully about this issue,” he continued. “Although we currently have treatments such as tricyclic antidepressants (eg, amitriptyline) and anticonvulsants (eg, pregabalin and gabapentin) that can result in pain relief, pharmacologic pain treatment is still ineffective in too many patients and we urgently need more effective therapies.”