Year two results from the Rio-Europe trial indicate that gains made in cardiovascular risk factors in the first year of treatment with rimonabant were maintained in the second year, according to a presentation at the annual meeting of the American College of Cardiology.

The RIO-Europe trial, a two-year phase III study with 1,507 patients, evaluated treatment with rimonabant, the first in a new class of therapeutic agents called selective CB1 Blockers.

The new data demonstrate that improvements in cardiovascular risk factors achieved with rimonabant 20 mg/day at the end of the first year of treatment were maintained in the second year. The study also demonstrated the safety and tolerability profile of rimonabant versus placebo.

Year two findings of the RIO-Europe trial are consistent with those of the other two-year trial in the rimonabant phase III program, RIO-North America, results of which were announced at the scientific sessions of the American Heart Association in November 2004.

"The RIO-Europe findings demonstrated that in addition to maintaining body weight loss, two-year treatment with rimonabant 20 mg/day compared with placebo reduced waist circumference, improved metabolic profile, and reduced the number of patients meeting the NCEP (National Cholesterol Education Program) criteria for metabolic syndrome, thus diminishing cardiovascular risk factors in patients studied," said Luc Van Gaal, MD, presenter.

RIO-Europe was a phase III, multinational multicenter, randomized, double-blind, and placebo-controlled trial comparing two fixed-dose regimens of rimonabant (5 mg and 20 mg once daily) to placebo for two years. The study was conducted with 1,507 patients at 40 centers in Europe and 20 centers in the US. The objectives of the trial were to assess the effects of rimonabant on weight loss for a period of one year and to determine rimonabant's potential to maintain weight loss during the second year. The study also assessed improvement in waist circumference and in metabolic risk factors (eg, dyslipidemia, glucose metabolism, and metabolic syndrome) and evaluated the safety and tolerability profile of rimonabant.

After a screening period of two weeks, patients were prescribed a hypocaloric diet (designed to reduce daily caloric intake by 600 kcal from the patients' energy requirements) and entered a four-week single-blind placebo run-in period. Afterward, patients were randomly assigned to one of the three treatment groups: rimonabant 20 mg or 5 mg or placebo for 104 weeks of double- blind treatment using a randomization ratio of 2:2:1.

The new findings demonstrated the two-year benefits of rimonabant 20 mg/day treatment vs placebo. Among patients completing the study, waist circumference was reduced by 7.5 cm (2.9 inches) in patients treated with rimonabant 20 mg/day for the full two year period vs. 3.4 cm (1.3 inches) for patients in the placebo group. Among all patients who entered the study, waist circumference was reduced by 5.7 cm (2.24 inches) and 1.8 cm (0.71 inches) in patients treated with rimonabant 20 mg/day and the placebo group, respectively.

Among patients completing the study, 59.7% of patients treated with rimonabant 20 mg/day lost more than 5% of their initial body weight vs 23.4%of those in the placebo group. Among all patients who entered the study, 44.4% of patients treated with rimonabant 20 mg/day lost more than 5% of their initial body weight vs 15.6% of those in the placebo group. Among patients completing the study, 32.1% of patients treated with rimonabant 20 mg/day lost more than 10% of their initial body weight, vs 10.9% of those in the placebo group. Among all patients who entered the study, 22.0% of patients treated with rimonabant 20 mg/day lost more than 10% of their initial body weight vs 6.3% of those in the placebo group.

Metabolic parameters such as HDL-cholesterol and triglycerides were significantly improved in patients treated with rimonabant 20 mg/day throughout the two-year period. Among patients completing the study, HDL-cholesterol increased by 28.2% in the rimonabant 20 mg/day group vs 16.8% in the placebo. Among all patients who entered the study, HDL-cholesterol increased by 22.6% in the rimonabant 20 mg/day group vs 12.6% in the placebo group.

Among patients completing the study, triglycerides were reduced by 8.8% in patients treated with rimonabant 20 mg/day throughout the two-year period vs an increase of 6.3% in the placebo group. Among all patients who entered the study, triglycerides were reduced by 4.1% in patients treated with rimonabant 20 mg/day vs an increase of 10% in the placebo group. A statistical analysis of the data suggested that approximately half of the improvements in HDL cholesterol and triglyceride profiles observed in patients treated with rimonabant 20 mg/day were independent of the weight loss achieved in this group.

Although people with diabetes were not included in the study, patients on rimonabant 20 mg/day showed improved insulin sensitivity as measured by HOMA (Homeostasis Model Assessment) compared with those on placebo. Of particular note is that the number of patients completing the study who met the diagnostic criteria for metabolic syndrome was reduced by approximately 50% in patients treated with rimonabant 20 mg/day vs a decrease of approximately 20.0% in the placebo group.