Investigational drug ups HDL by 27% in one year: linked to weight loss, improved smoking cessation, reversal of metabolic syndrome.(News)

MUNICH -- The investigational drug rimonabant, first in a new class of agents known as selective endocannabinoid type 1 receptor blockers, is looking more and more like the real deal: a potential blockbuster drug causing sustained weight loss in the obese, reversal of the metabolic syndrome, an improved cardiovascular risk profile, and increased success in smoking cessation.

Interim results of the randomized double-blind placebo-controlled 1,507-patient Rimonabant in Obesity-Europe (RIO-Europe) trial showed that after 1 year on 20 mg rimonabant/day, patients lost an average of 8.6 kg, reduced their waist circumference by 8.5 cm, boosted their cardioprotective HDL cholesterol levels by 27%, and lowered their triglyceride levels by 11%, Dr. Luc Van Gaal reported at the annual congress of the European Society of Cardiology.

"I have never before seen a 27% increase in HDL [cholesterol] with any drug--not statins, not even fibrates," observed Dr. Van Gaal, professor of internal medicine and diabetology at the University of Antwerp (Belgium).

At baseline, 42% of patients in the rimonabant 20-mg arm met criteria for metabolic syndrome, placing them at higher risk for cardiovascular disease. After 1 year of therapy in what will be a 2-year trial, the prevalence of the syndrome was cut by 53%.

RIO-Europe is a seven-nation study involving patients with a mean body mass index of 36 kg/[m.sup.2] and an average waist circumference of 110 cm. As is typical of obesity clinical trials, 80% were women.

Participants were encouraged by dietitians and counselors to modify their lifestyle by increasing physical activity and adopting a diet with a 600-cal/day deficit. One-fifth of subjects were randomized to placebo, while the remainder received either 5 mg or 20 mg of rimonabant daily.

The placebo response was high, which Dr. Van Gaal attributed to the counselors' dedication. Thirty-one percent of patients who completed 1 year of placebo therapy lost more than 5% of their initial body weight, and although that's an impressive figure, it is well below those of the rimonabant groups: 44% in the patients receiving 5 mg/day and a 67% rate in those receiving 20 mg/day.