patients who lost at least 5% of their baseline weight after 1 year were 51%, 33%, and 19% in the 20 mg, 5 mg, and placebo groups respectively. Waist circumference decreased 3.9 cm (p = 0.002 vs placebo) in the 5 mg group and 6.5 cm (p < 0.001 vs placebo) in the 20 mg group. Compared with placebo, 20 mg rimonabant led to statis- tically signiﬁcant increases in HDL-C (+22.3% vs +13.4%; p < 0.001) and decreases in total cholesterol to HDL-C ratio, triglycerides (–6.8% vs +8.3%; p < 0.0001), fasting glucose, fasting insulin, and insulin resistance (measured by the ho- meostasis model assessment [HOMA]); effects with 5 mg rimonabant did not reach statistical signiﬁcance compared with placebo except in HDL-C (+16.2% vs +13.4%; p = 0.048). Based on their statistical analysis, the investigators suggested that only approximately 50% of the effect on triglycerides and HDL-C could be explained by weight loss, adding support to a weight-independent metabolic effect of CB-1 blockade. No signiﬁcant changes in systolic blood pressure, total cholesterol or LDL-C were apparent. In the 20 mg rimonabant group, the incidence of MetSyn decreased from a baseline of 42.2% to 19.6% after 1 year while only changing from 39.9% at baseline to 31.4% at 1 year in the placebo group. Table 2 illustrates the placebo subtracted change from baseline in the major meta- bolic variables measured at the completion of the study. Rimonabant in obesity – lipids (RIO-Lipids) In RIO-Lipids 1036 obese or overweight patients (BMI 27– 40 kg/m2) with dyslipidemia (deﬁned by elevated ratio of total cholesterol to HDL-C >4.5 in women or >5 in men or elevated triglyceride levels >1.69 to 7.90 mmol/L) were randomized to placebo, 5 mg or 20 mg of rimonabant daily for 1 year (Després et al 2005). Exclusion criteria were similar to the other trials but also included patients receiving pharmacological treatment for dyslipidemia in the 6 weeks preceding the trial. Approximately 60% of the participants were female and 62% completed the study. Race of the participants was not reported. Baseline mean age was 48 years, average weight was approximately 96 kg, and average BMI was about 34 kg/m2. In ITT-LOCF analysis, the 5 mg group decreased weight by 3.1 kg (p < 0.001 vs placebo) and the 20 mg group decreased weight by 6.9 kg (p < 0.001 vs placebo). The proportion of patients who lost at least 10% of their weight after 1 year was 33% in the 20 mg group and 7% in the placebo group. Waist circumference in the 5 mg group decreased 3.5 cm (p = 0.029 vs placebo) and 7.1 cm (p < 0.001 vs placebo) in the 20 mg group. HDL-C increased 14.2% (p = 0.025 vs placebo) in the 5 mg group and 19.1% (p < 0.001 vs placebo) in the 20 mg group. The 20 mg group also showed signiﬁ- Vascular Health and Risk Management 2007:3(2) Rimonabant and cardiometabolic risk cant beneﬁcial changes in total cholesterol to HDL-C ratio, peak size of LDL-C particles, proportion of small LDL-C, triglycerides, and fasting insulin levels. Although there were no signiﬁcant differences between groups, total cholesterol increased modestly and LDL-C increased by about 7% in all three treatment groups. Systolic and diastolic blood pressure demonstrated a modest statistically signiﬁcant decrease in the 20 mg group compared with placebo. Subjects randomized to 20 mg rimonabant also demonstrated beneﬁcial effects on leptin and adiponectin levels that were not seen with placebo. In the 20 mg rimonabant group, c-reactive protein decreased from 5.0 to 4.1 mg/dL (p = 0.02 vs placebo) compared with only a modest decrease from 5.3 to 4.9 mg/dL in the placebo group. The 5 mg group did not show statistically signiﬁcant changes in any of these blood pressure, lipid, or neurohor- monal parameters. Table 2 illustrates the placebo subtracted change from baseline in the major metabolic variables mea- sured at the completion of the study. Rimonabant in obesity – North America (RIO-NA) In RIO-NA 3045 obese or overweight subjects were random- ized to placebo, 5 mg rimonabant or 20 mg rimonabant daily. Unique to RIO-NA following the ﬁrst year of treatment, pa- tients who received rimonabant were re-randomized to receive the same dose of rimonabant or placebo for a second year; subjects initially randomized to placebo remained on placebo for the full two years. Females composed 81% of the patients and 84% were white. Baseline average weight was approxi- mately 105 kg and BMI was about 38 kg/m2. Only 52.6% of participants completed the ﬁrst year of the study. Results in this trial were reported as placebo subtracted changes rather than the absolute values reported in the other trials. In the ITT-LOCF analysis, after one year placebo sub- tracted weight was reduced 1.3 kg (p < 0.001 vs baseline) in the 5 mg group and 4.7 kg (p < 0.001 vs baseline) in the 20 mg group. In the 20 mg rimonabant group 25% of subjects demonstrated at least a 10% weight loss compared with only 9% in the placebo group. The 20 mg group had statistically signiﬁcant placebo subtracted improvements in waist cir- cumference (–3.6 cm; p < 0.001) and triglycerides (–13.2; p < 0.001%). Placebo subtracted HDL-C improved 2.3% in the 5 mg group (p = 0.01 vs baseline) and 7.2% (p < 0.001 vs baseline) in the 20 mg group. Total cholesterol to HDL-C ratio also improved signiﬁcantly in both treatment groups. Fasting insulin level decreased (1.7 Uµ/mL in the 5 mg group and 2.8 µU/mL in the 20 mg group) and insulin resistance as measured by HOMA improved (Table 2). Prevalence of 185