The aftermath of fen/phen: Obesity still not treated as a chronic disease
FDA guidelines for diet drug users prevent problems
Last fall, many obese patients who thought they had found a magic bullet cure in fen/phen discovered that they may actually have bought themselves a ticket to heart disease. In light of alarming studies about the potential effects of the drugs, obesity specialists worried that the fallout would erase certain gains in the management of the disease. And of course, they worried about the safety of the patients for whom they had prescribed the troubled combination of fenfluramine (Pondimin) or dexflenfluramine (Redux) and phentermine (Ionamin, Adipex-P).
Six months later, with Pondimin and Redux off the market and patients under close watch, they're less worried about their patients' safety but still bothered by the public perception that fat people ought to just quit eating so much and get off their couches.
"We were making great strides in the last few years in getting people to see obesity as a chronic disease, and then we got stopped in our tracks with the fen/phen controversy. I think it set us back," says Richard A. Dickey, MD, vice president of the American Association of Endocrinologists and chairman of its obesity task force. Dickey is in private practice in Hickory, NC.
The fact is, Dickey says, some obese people could eat and exercise just right and still not lose enough weight. Many others simply can't make the necessary behavioral changes. And that means not only will they continue to be overweight, but they'll also keep increasing their risk for potentially devastating comorbid conditions such as diabetes and hypertension.
That's why fen/phen was so alluring for people constantly fighting the weight battle. Roughly 50 million Americans tried the drug combination, many with great success, until reports came from the Mayo Clinic that 24 patients had developed rare valvular disease. The Rockville, MD-based U.S. Food and Drug Administration began receiving more reports of similar problems in patients who took fen/phen and some who were taking only fenfluramine or dexfenfluramine. Further study found that 30% of patients evaluated had abnormal echocardiograms. Redux and Pondimin were both withdrawn from the market by Philadelphia-based Wyeth-Ayerst Laboratories, and the company set up an expert panel to evaluate the data on the drugs and recommend additional actions to address the situation. (For information on new weight-loss drugs, see related story, p. 50.)
The problem, says FDA medical officer Eric Colman, MD, is that it isn't known whether it was the combination of the drugs that led to valvular disease or whether each drug has that potential on its own. It's also unknown if stopping the drugs eliminates the problem or if patients will have long-term complications. What is known is that the fen/phen combination was never approved by the FDA. "The recent craze of combining the two and taking them long term was clearly off-label," Colman says. "They were never FDA-approved to be used together or to be used beyond a few weeks. Clearly, people were not taking it according to the way it should have been prescribed."
The FDA has issued interim guidelines for patients who have taken fen/phen:
· Patients who took fen/phen should get an echocardiograph exam if they have any signs or symptoms of heart or lung disease such as a new heart murmur or shortness of breath.
· An echocardiogram should be strongly considered for any patient who has taken these drugs, regardless of whether they have signs and symptoms, before undergoing a surgical or dental procedure. Patients with valvular heart disease are at increased risk of bacterial endocarditis following a medical or dental procedure.
· Patients should undergo a complete physical examination and medical history to check for signs and symptoms of valvular heart disease.
Dickey says those recommendations are adequate to prevent further problems. The American Association of Clinical Endocrinologists, under his leadership, is in the process of revising its obesity position statement to include the FDA guidelines. The AACE statement, when published this summer, will emphasize the importance of following fen/phen patients closely and will also recommend that patients sign consent forms when they enter weight-loss programs involving long-term pharmacotherapy. (For more ideas on obesity management, see related story, above.)
Xavier Pi-Sunyer, MD, director of endocrinology at St. Luke's Roosevelt Hospital in New York City, says he plans to see his patients who took fen/phen every six months for a complete physical. He says he hasn't seen anywhere near the 30% rate of valve problems that was published and that he doesn't think any of his patients are in trouble. What he doesn't want to see is fear of using drugs in obesity treatment.
"For some people, lifestyle modification is not enough," Pi-Sunyer says. "It's the same kind of indication as you have with an antihypertensive drug in a hypertensive patient. You start with diet and exercise and see if you can get the blood pressure down. If that doesn't work, you add a drug. If that doesn't work, you add two drugs."
Pi-Sunyer and Dickey agree that weight-loss drugs are needed in the treatment of obesity and outweigh the risks when used properly.
"If you want to continue chronic therapy, you have to pick something. You just have to be cautious," Dickey says. "Obesity is a chronic disease like diabetes or hypertension. You can't treat it for a few weeks and expect the disease to be gone when you stop. It doesn't go away."
Pi-Sunyer says he doesn't understand why people don't see obesity as a disease. "Obesity causes a lot of morbidity and mortality. It's not easy to do something about it. There's kind of a Puritan image that people should be able to lose weight on their own. The fact is, for whatever reason, these people are unable to do this."
And when they can't lose weight, the obesity itself might be the least of their problems. A recent study1 found that obesity is associated with significantly higher health care expenditures. Charles Quesenberry Jr., PhD, and colleagues from Kaiser Permanente in Oakland, CA, surveyed 17,118 Kaiser patients. They found that:
· Severely overweight people (body mass index of 35 or greater) had a 24% higher rate of outpatient visits than those of normal weight, and moderately overweight people (BMI of 30 to 34.9) had a 17% higher rate.
· Annual hospital days were 74% higher among the severely overweight and 34% higher among the moderately overweight.
· Pharmacy costs were 78% higher for the severely overweight and 60% higher for the moderately overweight.
The study says that the prevalence of obesity is increasing in the United States and that total direct costs of obesity-associated diseases were estimated at 6.8% of all health care expenditures in 1990.
One solution is for more insurance companies to pay for obesity prevention, Dickey says. "They end up paying for the comorbidities and complications instead of the obesity. We could wipe out more than half of Type II diabetes in the United States if we could wipe out obesity. How can anybody ignore the fact that obesity is costly? These people may be alive, but they don't have legs or they're blind. It's quality of life that is so important in terms of whether a treatment is helpful to the patient."
[For more information, contact Richard A. Dickey, MD, 415 North Center St., Suite 203, Hickory, NC 28601. Telephone: (704) 322-7338. Eric Colman, medical officer, U.S. Food and Drug Administration, Rockville, MD. (301) 827-1243. Xavier Pi-Sunyer, director of endocrinology, St. Luke's Roosevelt Hospital in New York City. Telephone: (212) 523-4161.]Reference
1. Quesenberry C, et al., Obesity, health services use, and health care costs among members of a health maintenance organization. Arch Intern Med 1998; 158:466-472.