Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia

Abstract

Rimonabant, a selective cannabinoid-1 (CB1) receptor antagonist, has been shown to reduce weight and enhance improvements in cardiometabolic risk parameters in Western populations. This study assessed these effects of rimonabant in Asian population. A total of 643 patients (BMI 25 kg/m2 or greater without diabetes) from China, Republic of Korea, and Taiwan were prescribed a hypocaloric diet (600 kcal/day deficit) and randomized to rimonabant 20 mg (n = 318) or placebo (n = 325) for 9months. The primary efficacy variable was weight change from baseline after 9 months of treatment. Results showed that rimonabant group lost more weight than placebo, (LSM ± SEM of −4.7 ± 0.3 kg vs. −1.7 ± 0.3 kg, P < .0001). The 5% and 10% responders were 2 or 3 folds more in the rimonabant group (53.0% vs. 20.0% and 21.5% vs. 5.7%, resp.) (P < .0001). Rimonabant also significantly increased HDL-cholesterol, decreased triglycerides and waist circumference,by 7.1%, 10.6%, and 2.8 cm, respectively (P < .0001). This study confirmed the comparable efficacy and safety profile of rimonabant in Asian population to Caucasians. Owing to the recent suspension of all the CB1 antagonists off the pharmaceutical market for weight reduction in Europe and USA, a perspective in drug discovery for intervening peripheral CB1 receptor in the management of obesity is discussed.

CB1 receptor antagonists: new discoveries leading to new perspectives

“…Psychiatric disorders were exclusion criteria, and side effects were evaluated by the Hospital Anxiety and Depression Scale (HAD). This study confirmed the efficacy and good tolerability of rimonabant (Pan et al 2011). RIO-Europe and RIO-North America were 2-year studies including overweight and obese adults.…”

“…In all cases, patients were also prescribed a hypocaloric diet and advised on increased physical activity. The 9-month RIO-Asia study evaluated the efficacy and safety of 20 mg rimonabant in obese Asian population (643 patients), who has a greater body fat content at lower BMI compared with Caucasians (Pan et al 2011). Four double-blind trials compared rimonabant 5 mg or 20 mg daily with placebo in 5500 overweight and obese non-diabetic patients (RIO-Lipid, RIO-North America, RIO-Europe) and in 1047 patients with type 2 diabetes (RIO-Diabetes).…”

“…The STRADIVARIUS study showed a significant effect on body weight, but no significant changes in the primary endpoint (percent atheroma value), but demonstrated normalized atheroma volume, as a secondary endpoint (Nissen et al 2008, Rosenstock et al 2008. The 9-month RIO-Asia study evaluated the efficacy and safety of 20 mg rimonabant in obese Asian population (643 patients), who has a greater body fat content at lower BMI compared with Caucasians (Pan et al 2011). This study confirmed the efficacy and good tolerability of rimonabant (Pan et al 2011).…”

Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin up-titration in Chinese patients with type 2 diabetes mellitus: study design and rationale of the vision study

“…In comparison with Caucasians, Asians have higher body fat at lower BMI levels and are thus more prone to obesity and related disorders such as diabetes mellitus, dyslipidemia, and hypertension at a lower BMI [48]. Consequently, in China, the BMI cut-offs for ‘overweight’ (24 kg/m 2 ) and ‘obesity’ (28 kg/m 2 ) are lower than those of the WHO criteria, and the population aged 60 years or more is defined as ‘elderly’ [49].…”

Obesity and the Endocannabinoid System: Is There Still a Future for CB1 Antagonists in Obesity?

“…In particular, overweight and obese patients have been included in the different Rimonabant in Obesity programs (RIO-Europe, RIO-Lipids, RIO-North America, RIO-Diabetes and RIOAsia), displaying a significant body weight loss, waist circumference reduction and an improvement of cardiovascular risk factors at the end of these clinical trials with no differences between Caucasian and Asian ethnic groups [91][92][93][94][95]. Rimonabant reached the market after successful trials revealing both metabolic benefits and body weight reduction in overweight and obese subjects [91,92].…”