Aug. 29, 2003 (Paris) -- A drug that was approved as an anti-epileptic but has gained a reputation as a neurological "jack of all trades" also appears to show promise in treating people with diabetes, researchers reported here yesterday at the 18th International Diabetes Foundation Congress.
"We think that most of the effect in diabetes is due to topiramate's ability to help individuals lose weight," said Kaj Stenlof, MD, a scientist at the Pennington Research Center in Baton Rouge, Louisiana.
In a clinical trial performed in 20 Swedish hospitals, Dr. Stenlof was able to demonstrate that topiramate, when prescribed to newly diagnosed patients with type 2 diabetes, was effective for weight loss. Patients lost about 6.6% to 9.1% of body weight using different doses of topiramate.
Although planned as a 52-week study, the trial was prematurely terminated by the manufacturer in order to implement a new formulation of topiramate designed to reduce adverse effects seen in the trial.
The most significant adverse effect, said Dr. Stenlof, was paresthesias, numbness in the fingers. The condition was reversible when the drug was discontinued and the cases were mild. He said that patients who needed fine tactile discrimination in their fingers for their work were unable to continue the trial.
Dr. Stenlof and colleagues had enrolled 541 patients in the placebo-controlled trial, which also emphasized dietary control and other behavioral intervention.
"There is no doubt that topiramate is effective in helping people lose weight," said Donald Chisholm, MD, professor of medicine at the University of New South Wales in Sydney, Australia.
"We also have seen that the side effect profile with topiramate does not appear to be a problem for most patients," he said while reviewing Dr. Stenlof's poster presentation. "However, no one is really too sure what the mechanism of action is for these effects we have seen in topiramate, and I think that has to be worked out."
Over the past few years, researchers have reported varying degrees of success in using topiramate off label to investigate treatment of essential tremor, for migraine prevention and treatment, managing weight gain caused by antidepressant medication, neuralgia form and other types of headaches, certain forms of anxiety disorders, treatment of alcohol dependence, and control of eating disorders such as bulimia, among other disorders.
Martin Fitchet, MD, senior director of clinical research at Johnson & Johnson Pharmaceutical Research and Development in Raritan, New Jersey, said that the company is preparing to seek Food and Drug Administration indications for topiramate in several areas. He noted that the research on topiramate presented in Paris are phase III clinical trials.
In a separate study at the meeting, which was also supported by Johnson & Johnson, researchers found that after 60 weeks of treatment, 81 obese, nondiabetic patients receiving topiramate had significantly reduced mean body weight for three different doses of the drug compared with 17 patients receiving placebo. Fat distribution was also significantly reduced in visceral organs of the abdomen.
The most common adverse effects in the study were paresthesia and difficulty concentrating at rates higher than those seen in patients receiving placebo, said lead author Tess Van der Merwe, MD, from Johannesburg General Hospital in South Africa.
Patients in the placebo group lost about 3.4% of body weight, while patients in the topiramate group lost between 8.3% and 14.9% of weight — the differences were statistically significant, Dr. Van der Merwe said.
The weight loss seen in these studies is associated with major endocrine changes. "You don't need a lot of weight loss — maybe 7% to 10% — for you to see a lot of difference," said Lais Monzillo,MD, from the Federal University Hospital in Sao Paolo, Brazil.
In her study, patients with insulin resistance syndrome who lost an average of 7.1% of their weight while on a six-month diet and exercise program had a 56.8% improvement in insulin sensitivity index.
"Weight loss is the driving force associated with reducing risk in diabetes," said Peter Hammam, MD, reporting for the Diabetes Prevention Program Coordinating Center at George Washington University in Washington, D.C. "For every kilogram of weight lost there is a 13% reduction in the risk of diabetes."
Noted Robin McCarthy, diabetes program manager at the Indian Health Council, Inc., in Pauma Valley, California, "It's amazing how losing just a little weight can go such a long way in preventing diabetes."
18th IDF Congress: Abstracts 1896, 1897, 1908, 103, 2760. Presented Aug. 28, 2003.
Reviewed by Brunilda Nazario, MD
Ed Susman is a freelance writer for Medscape.
Medscape Medical News © 2003 Medscape
Cite this: Topiramate Effective for Weight Loss in Diabetic Patients - Medscape - Aug 29, 2003.