The investigational diet drug Acomplia (rimonabant) has staying power for weight loss and slimmer waists, and can improve lipids.
That was the positive news.
The downside in the results of the Rimonabant in
Obesity (RIO) North America trial, reported in the Feb. 15
issue of the Journal of the American Medical Association, was
that half the patients quit taking the drug before the
two-year study was completed.
So Acomplia, which has been widely touted a
revolutionary diet drug, seems stymied by the same problem
faced by all diet medications-that patients are unwilling to
stick with the drug for the long haul.
Investigators for the
RIO-North America trial wrote that 51% of the patients
assigned to 20 mg of Acomplia daily dropped out after a year
of treatment and 76 of the 333 patients assigned to the 20 mg
dose for a second year also discontinued treatment.
And that dropout rate occurred despite the fact that a year of
treatment with 20 mg of Acomplia was associated with an
average weight loss of almost 14 pounds and a waist reduction
of 2.4 inches, versus just under four pounds and less than an
inch in the placebo group (P<0.001 for both).
Moreover, patients treated with 20 mg of Acomplia and calorie
reduction for a year increased HDL cholesterol by 12.6% versus
a 5.4% increase in the placebo arm (P<0.001) and decreased
triglycerides by 5.3% versus a 7.9% increase for patients
taking placebo (P<0.001).
In the year two, 40% of patients maintained on 20 mg achieved
"a weight loss of 5% or greater" compared to 19% of patients
in the placebo arm (P<0.001) and 17% achieved weight loss of
10% or more versus 8% in the placebo arm (P<0.001).
Moreover, after two years patients taking 20 mg of Acomplia
were able to maintain a waist measurement that was about two
inches smaller than baseline measurements, compared with a
reduction of just 0.87 inches for those in the placebo arm
(P<0.001).
Nonetheless, the high attrition rate led F. Xavier Pi-Sunyer,
M.D., of the obesity center at St. Luke's-Roosevelt Hospital
here and colleagues to conclude that more study is needed to
finally confirm a long-term benefit for Acomplia, which is a
cannabinoid-1 receptor blocker.
The RIO-North America, which is one of a trio of RIO phase III
trials (including RIO-Lipids and RIO-Europe), recruited 3,045
volunteers with a BMI of more than 27 as well as hypertension
and dyslipidemia. Randomization occurred between August 2001
and April 2004.
After a four-week placebo-plus-reduced calorie diet
(participants were instructed to cut their normal daily
caloric intake by 600 calories) run in, patients were
randomized to placebo, 5 mg Acomplia, or 20 mg of Acomplia for
a year.
For year two patients in the two Acomplia arms were
re-randomized to the same Acomplia dose or to placebo.
Patients originally randomized to placebo continued on
placebo.
Six hundred and two of the original 1,216-patient 5 mg
Acomplia group were re-randomized for year two, as were 660 of
the original 1,222 patients assigned to 20 mg of Acomplia,
while 299 of the original 607 placebo patients continued into
year two.
The final analysis included 292 patients from the original
placebo arm.
In addition, there were data from 590 patients in the 5 mg
arm-including 294 placebo patients-and from 651 patients in
the 20 mg arm, including 323 who were randomized to placebo
for year two.
In an editorial that accompanied the study, Denise G.
Simons-Morton M.D., Ph.D. and colleagues of the National
Heart, Lung, and Blood Institute in Bethesda, Md., wrote that
an "overriding concern is the failure to obtain final weight
measurements on about half of the randomized participants."
They noted that the dropout rate in the RIO-North America
trial was similar to that reported for other weight loss drugs
such as Xenical (orlistat) and Meridia (sibutramine). By
contrast, a meta-analysis of life-style intervention trials
reported an average drop-out rate of less than 5%.
The RIO-North America investigators reported that the most
significant side effect was nausea (about 11% of the Acomplia
group, versus 5.8% of the placebo group).
But, the editorial writers pointed out that patients taking 20
mg of Acomplia reported a 2.7-fold increase in the rate of
psychiatric disorders than those taking placebo.
Drugs like Acomplia should be considered within a broader
context that includes lifestyle modifications and "their
current role should be limited pending further evidence," said
the editorialists.
The RIO-North America trial was supported by Sanofi-Aventis,
which is developing Acomplia.
Primary source: Journal of the American Medical Association (Medpagetoday)