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Drug pipeline for obesity holds 189 contenders.

ORLANDO, FLA. -- Drugs in development will soon offer more hope to patients struggling to control their weight, Louis Aronne, M.D., said at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

The future of antiobesity medication therapy may include agents that block multiple pathways for weight gain, as well as novel drug combinations, said Dr. Aronne of the department of medicine at Weill-Cornell Medical Center, New York.

Behavior modifications remain the first approach to weight loss, but if unsuccessful after 6 months, pharmacologic treatment should be considered, according to guidelines from the National Institutes of Health.

Patients should be counseled that health benefits imparted by even small decreases in weight are worthwhile in terms of improvements in blood pressure, insulin sensitivity, and dyslipidemia. Otherwise, patients might be disappointed with the typical 5%-15% weight loss afforded by orlistat (Xenical) and sibutramine (Meridia), the two agents approved by the Food and Drug Administration for long-term weight loss.

The two available agents are not free of side effects. The main complaint with orlistat is its GI effects. Some patients taking orlistat experience oily spotting, liquid stools, fecal urgency, flatulence, and abdominal cramping. Evidence suggests that coadministration of psyllium mucilloid reduces these effects, Dr. Aronne said.

With sibutramine, potentially significant blood pressure increases are a concern, he said, so the drug is contraindicated in patients with uncontrolled hypertension. Minor effects include headaches, constipation, fatigue, and dry mouth.

Phentermine (lonamin, Fastin, Adipex) is approved only for 12-week, short-term weight loss. "I'd love to see one of the pharmaceutical companies do a long-term trial with phentermine. I think it would look really good," Dr. Aronne said.

"We need more drugs that are as good as the three or four drugs we have now," he said. Some patients do great on phentermine, others on orlistat. "We need more treatments because it's not a one-drug-treats-all situation."

Weight is controlled by a complex feedback system. "The plateau phenomenon we see all the time is not caused by bad behavior; it is caused by the weight mechanism we cannot yet control," Dr. Aronne said. "That is why most of our treatments cause 5%-10% weight loss--that is how much wiggle room we have. And that is why combination therapy seems to work better."

There are 189 antiobesity drugs in development. Some of these agents target hormones released by abdominal adipose tissue. Visceral fat produces many hormones that can contribute to disease risks. For example, elevated angiotensinogen levels can cause hypertension; resistin can increase the risk of type 2 diabetes mellitus; plasminogen activator inhibitor type 1 increases the risk of thrombosis. "High levels of leptin are associated with inflammation, thrombosis, and other parts of the pathology of obesity," Dr. Aronne said.

Two drugs approved for treating epilepsy, topiramate (Topamax) and zonisamide (Zonegran), have been assessed for an off-label effect on weight loss. Topiramate has shown some success in people with binge eating. "Talk to your local psychiatrist and neurologist before use--there are side effects, including CNS and cognitive symptoms," he said. Zonisamide has led to good weight loss as a second-line agent, but there are also side effects to consider. "Look for a good result, not a perfect result. You're going to run into side effects."

An agent approved for treating type 2 diabetes, metformin (Glucophage), was associated with modest weight loss, compared with placebo in a study (N. Engl. J. Med. 2002;346:393-403). Metformin may someday prove useful as an adjunct to prevent diabetes in insulin-resistant, obese patients.


Miami Bureau
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Title Annotation:Across Specialties
Author:McNamara, Damian
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Dec 1, 2004
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