Abstracts

RATIONALE: As the prevalence of diabetes mellitus increases, neurologists can expect to see more patients with both epilepsy and diabetes. Although AED effects on neuroendocrine function and/or body weight could influence metabolic abnormalities associated with diabetes, the impact of AEDs on diabetes has not been widely reported on, despite the fact that AEDs have been used to treat pain in patients with painful diabetic polyneuropathy. Many AEDs are associated with weight gain, which can increase the risk of type 2 diabetes. Topiramate (TPM) has been associated with weight loss and improvements in metabolic parameters (eg, glucose, insulin, lipids) in adults. In an animal model of diabetes mellitus, TPM had antidiabetic effects independent of body weight changes. Nearly 900 diabetic patients with peripheral polyneuropathy were treated with TPM in 3 double-blind, placebo-controlled studies to evaluate the effects of TPM on neuropathic pain, thereby providing the data we report here on diabetic control and weight in TPM- and placebo-treated patients.
METHODS: Adults (18-75 yrs) were eligible for randomization if they had painful diabetic peripheral polyneuropathy for [gte]6 mos and Hb[sub]A1c[/sub][lt]11% for [gte]3 mos before randomization. After a baseline period of up to 28 days, patients were randomized to treatment with placebo or TPM 100, 200 or 400 mg/day. Duration of double-blind treatment was 18-22 wks (titration to target dose, 6-10 wks; maintenance, 12 wks).
RESULTS: Across the 3 studies, 384 patients were randomized to placebo, 253 to TPM 100, 372 to TPM 200, and 260 to TPM 400 (TPM total, 885). Most patients had type 2 diabetes (placebo, 82%; TPM, 81%). Mean Hb[sub]A1c[/sub] among TPM-treated study completers was reduced 0.4-0.5%, TPM 100; 0.7 - 0.8%, TPM 200; and 0.5 [ndash] 0.6%, TPM 400; in the placebo groups, mean changes were between -0.2 and +0.2%. Hb[sub]A1c[/sub] changes were statistically significant for TPM vs. placebo. Among study completers, the proportion of patients with [gte]0.5% and [gte]1.0% reductions in Hb[sub]A1c[/sub] levels were: placebo, 32% and 15%, respectively; TPM 100, 55% and 18%; TPM 200, 57% and 38%; TPM 400, 62% and 50% (TPM overall, 57% and 38%). Mean body weight was increased 0.3-0.9% in the placebo group and reduced 2.1-5.1% with TPM, depending on TPM dose. Changes in Hb[sub]A1c[/sub] correlated poorly with changes in weight. The most common adverse events in TPM-treated patients ([gte]5% incidence vs. placebo) were paresthesia (placebo, 5% vs TPM, 12%), nausea (7% vs. 12%), somnolence (4% vs. 10%), anorexia (3% vs. 10%), fatigue (11% vs. 16%) and weight loss (1% vs. 7%).
CONCLUSIONS: In diabetic patients, TPM improves diabetic control as measured by Hb[sub]A1c[/sub] levels. Because reductions in Hb[sub]A1c[/sub] levels do not correlate with TPM-induced weight loss, the effect of TPM on glycemic control appears to be independent of weight loss. The favorable weight and metabolic profile of TPM, combined with its effectiveness against partial and generalized seizures, make TPM a particularly beneficial option for the growing number of diabetic/overweight patients with epilepsy.
[Supported by: Johnson & Johnson Pharmaceutical Research & Development]; (Disclosure: Salary - Johnson & Johnson Pharmaceutical Research & Development)