New approaches for the management of patients with multiple cardiometabolic risk factors.

Abstract

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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