Therapeutic strategies currently available for the management of cardiometabolic risk factors focus mainly on individual factors, and do not target the underlying cause of cardiovascular and metabolic diseases. The Rimonabant-in-Obesity (RIO) programme consists of four 1-2 yr Phase III trials, RIO-Europe, RIO-Lipids, RIO-North America (NA), and RIO-Diabetes, designed to assess the efficacy and safety of rimonabant in the treatment of multiple cardiometabolic risk factors in 6600 overweight/obesity patients. After 1 yr, results from the RIO-NA anci RIO-Europe trials, showed that treatment with rimonabant 20mg/day improved HDL-C (p< 0.001), triglycerides (p< 0.001), fasting insulin (p< 0.001) and insulin resistance (p=0.002 and p< 0.001 for RIO-Europe and RIO-NA, respectively) compared to placebo. The results of both studies also showed significant and sustained mean reductions in waist circumference (p< 0.001), and weight (p< 0.001) for rimonabant 20 mg/day compared with placebo. Similar improvements were seen in the RIO-Lipids trial at 1 yr and these results were consistently maintained over 2 yr in RIO-NA. The RIO-Europe and RIO-NA trials showed that improvements in HDL-C and TG levels with rimonabant over 1 yr, compared with bodyweight, were beyond that attributable to weight loss alone [40 and 55% for HDL-C and triglyceride (TG), respectively for RIO-Europe and 58 and 47%, respectively for RIO-NA]. Additionally, in RIO-NA, changes in fasting insulin and homeostasis model assessment insulin resistance (HOMA-IR), were beyond weight loss alone (50 and 51%, respectively). Rimonabant was well tolerated and the majority of adverse events reported were mild and transient, and occurred early in the treatment period. Rimonabant, the first cannabinoid receptor type 1 (CB1) receptor blocker, reduces weight and waist circumference, and improves lipid and glucose metabolism.
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