New Weight-Loss Drugs Pass First Tests

More Pounds Lost With Epilepsy Drug Zonegran, New Satiety Drug Axokine

Reviewed by Michael W. Smith, MD on April 08, 2003
From the WebMD Archives

April 8, 2003 -- Two new weight-loss drugs may help obese people, clinical trials suggest.

The findings come in two separate reports. In the first study, obese people lost 13 pounds after 16 weeks of adding the epilepsy drug Zonegran to a low-calorie diet. In the second study, the optimal dose of the experimental drug Axokine helped obese people lose nine pounds in 12 weeks. Both studies appear in the April 9 issue of TheJournal of the American Medical Association.

Zonegran is already FDA approved. It's used to treat epilepsy. During clinical trials, epilepsy patients treated with the drug lost weight. That was bad for them -- but it might be a good weight-loss drug.

Duke University researchers led by Kishore M. Gadde, MD, put 60 obese volunteers on a low-calorie diet. Half also got Zonegran; the others got a look-alike placebo. After 16 weeks, those who got only the diet lost about two pounds. But those getting Zonegran lost an average of 13 pounds. Side effects -- mostly fatigue -- were mild. However, Zonegran is known to cause dizziness, impaired thinking, and sleepiness in epilepsy patients. It's also been linked -- rarely -- to kidney stones. Zonegran's manufacturer, Elan Biopharmaceuticals, provided the drug for the study.

More weight-loss news from a special obesity issue of The Journal of the American Medical Association.

Weight-Loss Programs Keep Pounds Off

Jury Still Out on Low-Carbohydrate Diets

Obese Children Suffer Like Cancer Kids

Watching TV Instead of Your Waistline?

"The results of this short-term study provide preliminary evidence that [Zonegran], in conjunction with diet, can be more effective than diet alone for obese patients seeking to lose weight," Gadde and colleagues write.

Axokine is a brand new drug with hopes of being a totally different kind of weight-loss drug. It's a man-made chemical that mimics a chemical the brain makes to protect itself from injury. It was designed as a possible treatment for Lou Gehrig's disease. But when researchers gave the experimental drug to patients, they lost weight.

Later experiments showed why. The drug affects a powerful brain system called the leptin pathway. Leptin is a chemical messenger that tells you when you've had enough to eat. Obese people have leptin resistance; they lose the ability to know when they're full. Axokine apparently bypasses this resistance and flips the fullness switch.

Mark P. Ettinger of Regeneron Pharmaceuticals Inc. in Tarrytown, N.Y., and colleagues performed the first study of Axokine's role as a weight-loss drug in obese people. They put 173 of these volunteers on a low-calorie diet. Some got fake placebo injections. Others got various injection doses of Axokine. The study was funded by Axokine's manufacturer, Regeneron Pharmaceuticals Inc.

After 12 weeks, those on the diet alone gained about a fifth of a pound. Those getting what turned out to be the best dose of Axokine lost an average of nine pounds.

Perhaps the best news came in the yearlong period after treatment. There was no immediate weight gain when drug treatment stopped. After about a year, patients treated with Axokine started to gain some weight.

There was a high rate of side effects reported for both the weight-loss drug Axokine and placebo. Side effects that appeared linked to Axokine treatment included skin reactions at the site of injection, nausea, and increased cough. These last two side effects weren't as much a problem in those who got the best dose of Axokine.

A large, ongoing phase III clinical trial is now delving further into Axokine's role as a safe, weight-loss drug in obese people.