If only ...

Deann SHANNON hears the comments frequently at the Curves fitness center in Orange. Even as people work up a sweat on the exercise machines, the topic of conversation will turn to diet drugs.

“I hear people say they’re going to buy this drug or that,” said Shannon, the owner of three Curves gyms, which cater exclusively to women. “Some people don’t like to exercise, and they would try anything. They’re looking for a quick fix.”

They’re not the only ones. A drug that would make weight loss easier is one of the most prized, but elusive, goals in medicine. And numerous pharmaceutical companies are working on diet drugs that could reach the market during the next decade. One company, Sanofi-Aventis, recently applied to the Food and Drug Administration for approval of a drug called Acomplia, which, if approved, would become the first new prescription obesity drug in six years.

But one thing is becoming painfully clear to researchers and drug companies: Previous efforts to produce a blockbuster diet drug have fizzled, and there is still no miracle remedy in sight. Recent studies of Acomplia (also known as rimonabant, its generic name) show that the drug, while potentially helpful, will not benefit everyone nor will it produce substantial weight loss in most people.

Instead, Acomplia’s role more likely would be as one of a number of diet drugs that not only aid weight loss but also address the medical consequences of obesity, such as diabetes and heart disease, say researchers. It’s likely that a combination, or cocktail, of obesity drugs will ultimately prove most beneficial.

“What most patients are starting to realize is that they need a little help,” said Dr. Ken Fujioka, director of the Nutrition and Metabolic Research Center at Scripps Clinic in Del Mar. “In our society, everything is set up against you when you’re trying to lose weight. And one-third of Americans are heavy enough that they are running into medical problems related to their weight.”

Two of three U.S. adults are classified as overweight or obese, according to federal figures, and drugs that help people lose weight could cut the rates of heart disease, diabetes, several types of cancer and gallbladder disease. A safe, effective pill to help people achieve a normal weight would increase life span, extend worker productivity and bring joy to many.

The last two prescription diet drugs to reach the market -- Meridia in 1997 and Xenical in 1999 -- were introduced with a lot of hype but have attracted only a modest following. Xenical blocks the absorption of some fat, but it causes diarrhea, bloating and gas in many people who take it. Meridia works by creating a sensation of fullness and curbing hunger, but it has been linked to increases in blood pressure and heart rate.

Doctors would love to have more options to help patients lose weight. There are only two prescription drugs to treat obesity, plus weight-loss surgery, contrasted with roughly 100 drugs to treat hypertension alone, said Dr. Louis Aronne, a professor of medicine at Cornell University’s Weill Medical College in New York.

“There is a huge gap in our armamentarium,” he said.

As recently as the 1980s, the only medications to help people lose weight were stimulants, which boost metabolism and suppress appetite. But stimulants are usually only effective for a short time, and they have been linked to side effects. The stimulant craze began to quiet in 1997, when the fen-phen drug combination was found to cause heart valve abnormalities, and more recently when the herbal stimulant ephedra was banned by the FDA last year due to safety concerns. (A ruling in April by a federal judge in Utah in favor of a dietary supplement company that had challenged the FDA ban has raised anew the question of whether the government’s action will stand.)

Researchers today are focused on understanding how the body regulates weight and how fat is produced and stored in the body. It will likely take many years before scientists really understand the biology of obesity, they say. For now, most experiments are done on mice, not humans. The development of Acomplia, however, suggests that progress is being made.

Acomplia is the first of a new class of drugs that affect signals in the brain that influence appetite. The compound blocks the cannabinoid receptor 1, which helps control hunger; these same receptors are stimulated when people smoke marijuana and get the “munchies.”

The overactivation of these receptors is thought to contribute to obesity and even nicotine and drug dependence. Preliminary studies on Acomplia for smoking cessation and alcohol and drug treatment are underway.

As an obesity treatment, Acomplia may be best suited for people who are not only overweight but also have metabolic syndrome. Metabolic syndrome is a collection of symptoms, including high blood pressure, high cholesterol, large waist circumference, obesity and insulin resistance, that can lead to diabetes and heart disease without treatment.

A study published in April in the Lancet, a medical journal, showed that 67% of people taking 20 milligrams of Acomplia achieved an overall weight loss of 5% after one year, and 39% of the participants achieved a 10% weight loss.

Acomplia also produced an average reduction of 1.6 inches in waist circumference and led to improvements in cholesterol levels (including HDL, or “good” cholesterol) and insulin resistance.

Waist circumference is increasingly seen as an important measure of cardiovascular health because intra-abdominal fat tends to be linked to heart problems more than fat distributed elsewhere on the body.

Overall, half of the patients with metabolic syndrome no longer had the condition after taking Acomplia for two years.

“This is a very good treatment for metabolic syndrome, and the effect is maintained,” said Aronne. “The way you should look at this new class of obesity treatments is that they are drugs that improve all of the complications of obesity -- and oh, by the way, you lose weight when you take them.”

But the drug has been found to have some significant side effects that could lower the odds of FDA approval. About 19% of the patients dropped out of the study due to depression, vomiting and nausea. Because of the possibility of a psychiatric side effect -- and because Acomplia is the first medication to act on the cannabinoid system in the brain -- the FDA may proceed with extra caution.

Future prescription obesity drugs could reflect a similar level of sophistication. Amylin Pharmaceuticals Inc. in San Diego said it was testing higher doses of its diabetes drug, Symlin, to determine if it could aid weight loss by enhancing the feeling of fullness when eating.

Another drug in early-stage trials, Arena Pharmaceutical Inc.’s APD356, works in the brain on specific serotonin receptors to help regulate food intake and metabolism. Studies are also underway on ghrelin, a peptide that regulates eating behavior. And scientists at Nastech Pharmaceutical Co. in Bothell, Wash., are in early-phase clinical trials for a nasal spray that acts to promote satiety.

But stumbles in obesity research are common. After more than a decade’s work, researchers are still trying to understand how the hormone leptin works to regulate weight. GlaxoSmithKline has shelved its studies on an appetite suppressant.

Obesity drugs will probably be best suited for people who need to lose a moderate amount of weight -- perhaps 30 pounds or more. “All these drugs give you a 5% to 10% weight loss. Beyond that it takes hard work,” said Fujioka.

For patients who need to drop less than 30 pounds, experts say that lifestyle changes, such as an improved diet and more exercise, are likely to be more effective. And for those who need to lose a great deal of weight -- about 100 pounds or more -- bariatric surgery is probably the best option for now, they say.

Moreover, it is likely that the impressive results of a drug, achieved during a short-term, carefully controlled research study, may be difficult to repeat in real life. Such drugs might need to be taken for years, be costly and not be covered under most health insurance plans, said Dr. Joseph Risser, director of clinical research at Lindora Medical Clinic in Costa Mesa.

In one study at Lindora, researchers followed the progress of people taking a weight loss drug that was partially covered by insurance. At the end of one year, only 10% of the participants were still taking the medicine.

Studies on Meridia and Xenical show both drugs can produce modest weight loss (an average of 11 pounds compared with a placebo) when combined with dietary recommendations.

“We see modest results in clinical trials, but in real life we found much less effective results because people were not complying,” in part because of the drugs’ cost, Risser said.

Medications may prove most successful simply as a way to jump-start a diet and exercise program, not as a long-term solution.

Jill Vaughn, a Yorba Linda woman who swims daily and goes to the gym three times a week, would be reluctant to replace her diet and exercise regimen with a pill or a shot. “I would wonder if the effects of the medication would last,” she said as she stopped by a Jenny Craig weight loss center one day recently.

Vaughn is happy with the results of her weight loss program, having already shed half of the 60 pounds she hopes to lose. After decades of dieting and trying about a dozen over-the-counter weight loss pills, she’s convinced that there is no simple solution.

“The old me was always looking for an easy way out,” she said. “But there is no easy way.”