Thursday, August 16, 2012

New Diet Pills Offer Option to Off-Label Obesity Drugs




By MELINDA BECK

July 30, 2012, 6:50 p.m. ET

Piper Miguelgorry started gaining weight in her 30s and 40s, after having three sons. The environmental researcher from Folsom, Calif., tried many diet regimes, without success, until she found a weight-loss center in nearby Roseville, where phentermine, a prescription appetite suppressant, was part of the plan, along with a high-protein, low-carb diet.

"Much to my surprise, I lost 50 pounds," says Mrs. Miguelgorry, 58, who has kept it off for more than a year. She also beat Type 2 diabetes and cut her cholesterol in half. She credits phentermine with helping reduce her craving for carbohydrates and plans to stay on it indefinitely.

 
Two diet pills just approved by the FDA, Qsymia and Belviq, won't be available for several months, but some doctors have been prescribing the ingredients of Qsymia (a migraine drug and phentermine, an old diet pill) to patients for years specifically for weight loss. Melinda Beck on Lunch Break explores the risks and side effects. Photo: AP.
Physicians who treat obesity hailed the Food and Drug Administration's recent approval of two new diet drugs—the first in 13 years—as a new era in weight-loss management. But some obesity specialists, including those at prestigious medical centers, have been prescribing medications to help patients lose weight for decades, both on and off-label.

Those medications include phentermine and several other stimulants approved for weight loss in the 1950s, as well as drugs to treat diabetes, depression and attention-deficit disorder that have weight-loss as a side effect.

One of the newly approved drugs, Qsymia, is a combination of phentermine and topirimax, a drug for easing seizures and migraines that also tends to make people feel full. The other, Belviq, works on brain receptors for serotonin, a neurotransmitter than triggers feelings of satisfaction.

Physicians can legally prescribe medications for uses not specifically approved by the FDA. But most obesity doctors do so cautiously given the history of diet pills removed from the market due to serious side effects including death.

"The fact that we've got two new drugs approved will reaffirm to the public that this truly is a medical problem and there's a place for pharmacotherapy," says Ed Hendricks, head of the Center for Weight Loss Management, which treated Mrs. Miguelgorry.

While some experts argue that people who are obese should simply eat less and exercise more, many physicians who treat obesity say it is driven by biological changes in the body, not lack of willpower.

"People say, 'Why are you treating a lifestyle problem with medication?' If you think that, you don't understand obesity," says Louis Aronne, director of the Comprehensive Weight Control Program at New York Presbyterian Hospital/Weill Cornell Medical College. He says there is mounting evidence that in some people, neurons in the hypothalamus that should recognize when the body has stored sufficient fat and either cut food intake or boost energy expenditure aren't working properly. Medications can help, says Dr. Aronne, who oversaw clinical trials of Qsymia.

In trials of 3,700 obese and overweight patients, those who took Qsymia for one year lost 6% to 9% more of their body weight than those on a placebo. Nearly 70% lost at least 5% of their weight.

With Belviq, of nearly 8,000 patients studied, those on the drug lost about 4% more than those on placebo. All were also counseled to exercise and eat a reduced calorie diet. The FDA says people who don't lose at least 5% of their weight in 12 weeks should discontinue the drugs.

People who eat very large portions or think about food all the time, even right after a meal, aren't getting biochemical signals to stop eating and may find drugs helpful, says Robert F. Kushner, clinical director of the Comprehensive Center on Obesity at Northwestern University.

People who eat for emotional reasons tend to benefit less, although drugs can help clarify their motivations. "If you give a medication that makes them feel full, but they still keep eating, it becomes very clear that it really is emotional," says Dr. Kushner, chairman of the American Board of Obesity Medicine.

The new drugs are FDA approved for patients with a body mass index of 30 or higher, or with a BMI of 27 and high blood pressure, diabetes, high cholesterol or sleep apnea. People with very large amounts of weight to lose may benefit more from bariatric surgery, or a combination, doctors say. The drugs aren't covered by most insurance companies. They are expected to be available this fall.

Most of the drugs currently prescribed for weight loss suppress appetite by affecting neurotransmitters, which send signals in the brain. Stimulant medications are among the most powerful. The FDA approved several stimulants—including phendimetrazine (marketed as Bontril) and diethylpropion (Tenuate)—specifically for weight loss in 1959. They remain on the market today.

How They Work

Drugs sometimes prescribed for weight loss work in various ways.

·         Stimulants rev up the central nervous system.

·         Antidepressant drugs such as buproprion (Wellbutrin) affect brain chemistry.

·         The diabetes drug metformin (Glucophage) reduces the impact of blood sugar. Liraglutide (Victoza) boosts a gut hormone to promote fullness.

·         The FDA-approved obesity drug orlistat (Xenical, Alli) blocks fat absorption.

·         Naltrexone (Depade, ReVia) blocks opiod receptors and makes food less appealing.

The best known is phentermine, half of the popular fen-phen combination in the 1990s until fenfluramine was linked to heart-value damage and discontinued in 1997. Because they are potentially addictive, phentermine and the others are approved for short-term use only. "But all of us use it long-term," says Dr. Kushner. Dr. Hendricks, who says he has treated 15,000 patients with phentermine, alone and in combinations, over 23 years, and says that patients who keep taking it tend to maintain their weight loss. Drs. Aronne, Hendricks and Kushner all consult for drug makers.

ADHD drugs including Ritalin and Adderall also suppress appetite in some patients, but most obesity doctors use older generic stimulants. Patients with heart disease, high blood pressure, hyperthyroidism or glaucoma should not use stimulants.

The diabetes drug Metformin helps decrease the amount of sugar the body absorbs from food and increases the body's response to insulin. Some patients can experience dangerously low blood sugar.

It is unclear why bupropion (Wellbutrin) doesn't make patients gain weight the way other antidepressants do, but it may help ease cravings. (Last month, GlaxoSmithKlein agreed to pay a $3 billion fine in part for promoting Wellbutrin for weight-loss and other off-label uses.)

Naltrexone (Depade, ReVia) helps alcoholics stop drinking by blocking opiod receptors in the brain, diminishing the kick booze provides. It may make food less rewarding the same way. Side effects, in rare cases, may include liver damage.

Some clinics promote human chorionic gonadotropin (hCG), an infertility treatment, as a way to "reset metabolism" when combined with a 500-calorie-a-day diet. But obesity experts say there is no evidence that hCG works better than a placebo. The FDA has warned seven companies to stop selling over-the-counter hCG and making unsupported claims.

Respected obesity experts say consumers should be wary of purported diet drugs sold over the Internet, as well as doctors who sell drugs from their offices, with little or no evaluation or without a comprehensive weight-loss plan.

Diet Drugs Over the Years

Medications the FDA approved, rejected or the makers withdrew

Years on the U.S. Market
Drug (Brand Name)
Comment

1949-1979
Amphetamine
Discontinued due to potential for abuse

1959-present
Phentermine and other anoretics
Appetite suppressants; approved for short-term use only

1960s


'Rainbow pills'
Amphetamine, digitalis, diuretics combined; discontinued after links to several deaths

1973-1997
Fenfluramine (Pondimin)
Often combined with phentermine in 'fen-phen'; withdrawn after links to heart value problems

1996-1997
Dexfenfluramine (Redux)
Similar to fenfluramine; withdrawn after links to heart value problems

1997-2010
Sibutramine (Merida)
Withdrawn due to risk of heart attack, stroke

1999-present
Orlistat (Xenical, Alli)
Blocks fat absorption

2007 (rejected)
Rimonabant (Acomplia)
Suspected link to suicidal thoughts

2011 (rejected)
Contrave
Combines an antidepressant and an alcoholism drug; now undergoing more trials

2012
Qsymia, Belviq
Approved after additional data submitted

A version of this article appeared July 31, 2012, on page D1 in the U.S. edition of The Wall Street Journal, with the headline: New Diet Pills Offer Option To Off-Label Obesity Drugs.



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