Wednesday, November 10, 2004 · Last updated 9:13 a.m. PT
Diet drug helps people keep weight off
By MARILYNN MARCHIONE
AP MEDICAL WRITER
NEW ORLEANS -- An experimental pill that offers the fairy-tale promise of
helping people lose weight and quit smoking has gathered even more
stardust.
The biggest test yet of the drug found that it helped people not only drop
pounds but also keep them off for two years - longer than any other diet
drug has been able to achieve. Cholesterol and other health measures
improved, too.
The impressive results from a study of more than 3,000 obese people were
presented at a medical conference Tuesday, capping months of anticipation
about the new drug, Acomplia, made by the French pharmaceutical firm
Sanofi-Aventis.
Doctors called the research exciting and the company, which funded the
study, thinks the drug, also known as rimonabant, could have blockbuster
potential similar to cholesterol-lowering statin drugs.
In a study of 3,040 obese people throughout the United States and Canada,
those given the higher of two doses of the drug lost more than 5 percent of
their initial body weight, and a third of them lost more than 10 percent.
"They achieved and maintained a weight loss of 19 pounds as compared to 5.1
pounds in the placebo group," said Dr. F-Xavier Pi-Sunyer of Columbia
University in New York, who led the research and presented results at the
American Heart Association conference.
Those who quit taking the pill in the second year of the study regained
most of what they'd lost, suggesting that people might have to take the
drug indefinitely to maintain a lower weight.
"We consider this to be a chronic problem. You don't cure obesity, you just
improve it," Pi-Sunyer said.
About two-thirds of American adults are overweight or obese, raising their
risk of everything from cancer and cardiovascular disease to sore joints
and snoring. About a fourth of American adults smoke, which brings many of
the same woes.
It's been devilishly difficult to develop effective treatments for either
problem. Diet drugs in particular have a checkered history, most notably
the withdrawal from the market in 1997 of the popular "fen-phen" drug
combination after users developed heart valve problems.
Drugs now on the market either are designed for short-term use or have
distasteful side effects like bowel problems that make many shy away from
them.
Acomplia's maker thinks it will avoid those problems by attacking obesity
in a novel way, and plans to seek federal approval for it next year.
It's the first diet drug aimed at blocking the "pleasure center" of the
brain and interfering with the cycle of craving and satisfaction that
drives many compulsive behaviors and addictions. This same circuitry is
activated when people smoke pot.
"Weight regulation is really kind of an addictive behavior," said Dr.
Robert Eckel, an expert on metabolism from the University of Colorado
Health Sciences Center who had no role in the study.
It involved people who either were severely obese or were moderately obese
and also had another heart-related health problem such as low "good"
cholesterol, high blood pressure, or high blood sugar.
They were given nutrition advice and urged to cut 600 calories a day from
their diet, and were randomly assigned to get either a 5- or 20-milligram
dose of Acomplia or fake pills. Neither they nor their doctors knew who had
received which.
After one year, those on the higher dose had lost an average of 19 pounds -
the same result found in two smaller studies of the drug reported earlier
this year.
The new study went on to test whether staying on the drug kept people from
regaining weight. Those who took Acomplia during the first year were
redivided to either continue on it or get fake pills for the second year.
At the end of the two years, 62.5 percent of people on the higher dose had
lost 5 percent of their body weight compared to 36.7 percent on the low
dose and 33.2 percent on fake pills.
Waistlines shrank 3.1 inches with the higher dose, 1.9 inches with the
lower one and 1.5 inches for those on fake pills.
HDL or "good" cholesterol rose 24.5 percent on the higher dose, 15.6
percent on the lower one and 13.8 percent on fake pills. Triglycerides also
fell according to dose.
"What we have here now is essentially a brand new mechanism to treat an
epidemic of staggering progression," said Dr. Douglas Greene, Sanofi's vice
president of regulatory affairs.
Most people in the study lost weight over six to seven months, then
plateaued. Researchers said that's probably the limit of what the drug can
do and that further weight loss should not be expected.
Some people on the drug had nausea, but it usually was short-lived. Rates
of anxiety and depression were no greater for those on Acomplia than those
getting fake pills.
"There was no evidence this drug over two years had something we had to
worry about in the way of safety," Pi-Sunyer said.
"The results are very encouraging. The safety profile looks good. It seems
like people tolerate the medication," said Dr. Sidney C. Smith Jr., a
University of North Carolina cardiologist who had no role in the study.
"It would be nice if this could be used as a jump-start" to get people to
permanently change lifestyle habits so they didn't have to depend on a drug
for the benefits, he said. "The more we can change behavior and modify risk
factors in that manner, the better."
The company has not yet said whether it will seek approval to sell the drug
for obesity and smoking cessation. The only study reported so far of
Acomplia in smokers lasted only 10 weeks and found that 28 percent on the
drug kicked the habit versus 16 percent on dummy medication. Two longer,
larger studies of this are in the works, along with another study of
Acomplia in diabetics.
"One drug may ultimately not get the job done," Eckel said. But he said the
results so far on obesity suggest "it could be an exciting new player in
the field."
Sanofi Aventis is the world's No. 3 pharmaceutical company by sales. It was
created by the merger earlier this year of Sanofi-Synthelabo SA and Aventis
SA.