[en] Rimonabant, the first selective CB(1) receptor antagonist in clinical use, has been extensively investigated in the Rimonabant in Obesity (RIO) programme, comprising four 1-2 year placebo-controlled randomised clinical trials recruiting more than 6600 overweight/obese patients with or without co-morbidities. Rimonabant 20 mg daily consistently reduced body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and increased HDL cholesterol concentrations in both non-diabetic and type-2 diabetic overweight/obese patients. Adiponectin levels were increased, an effect that correlated with HDL cholesterol augmentation, while small dense LDL cholesterol levels were decreased in patients receiving rimonabant 20 mg compared with those receiving placebo in RIO Lipids. Furthermore, in RIO Diabetes, a 0.7% reduction in glycated haemoglobin (HbA1c) levels was observed in metformin- or sulphonylurea-treated patients with type-2 diabetes, an effect recently confirmed in the 6-month SERENADE (Study Evaluating Rimonabant Efficacy in drug-NAive DiabEtic patients) trial in drug-naive diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. The positive effects observed after 1 year were maintained after 2 years. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared with placebo. In clinical practice, rimonabant has to be prescribed to the right patient, i.e. overweight/obese subjects with cardiometabolic risk factors and with no major depressive illness and/or ongoing antidepressive treatment, in order to both maximise efficacy and minimise safety issues. New trials are supposed to confirm the potential role of rimonabant in patients with abdominal adiposity, atherogenic dyslipidaemia and/or type-2 diabetes, i.e. at high cardiometabolic risk.
Disciplines :
Cardiovascular & respiratory systems Endocrinology, metabolism & nutrition
Author, co-author :
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Language :
English
Title :
CB1 receptor blockade and its impact on cardiometabolic risk factors: overview of the RIO programme with rimonabant.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Pagotto, U., Marsicano, G., Cota, D., Lutz, B., Pasquali, R., The emerging role of the endocannabinoid system in endocrine regulation and energy balance (2006) Endocr Rev, 27, pp. 73-100
Matias, I., Di Marzo, V., Endocannabinoids and the control of energy balance (2007) Trends Endocrinol Metab, 18, pp. 27-37
Cota, D., CB1 receptors: Emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health (2007) Diabetes Metab Res Rev, 23, pp. 507-517
Di Marzo, V., Bifulco, M., De Petrocellis, L., The endocannabinoid system and its therapeutic exploitation (2004) Nat Rev Drug Discov, 3, pp. 771-784
Pacher, P., Batkai, S., Kunos, G., The endocannabioid system as an emerging target of pharmacotherapy (2006) Pharmacol Rev, 58, pp. 389-462
Matias, I., Gonthier, M.P., Orlando, P., Martiadis, V., De Petrocellis, L., Cervino, C., Petrosino, S., Di Marzo, V., Regulation, function, and dysregulation of endocannabinoids in models of adipose and β-pancreatic cells and in obesity and hyperglycemia (2006) J.Clin Endocrinol Metab, 91, pp. 3171-3180
Cote, M., Matias, I., Lemieux, I., Petrosino, S., Almeras, N., Després, J.P., Di Marzo, V., Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men (2007) Int J Obesity, 31, pp. 692-699
Després, J.P., Lemieux, I., Abdominal obesity and metabolic syndrome (2006) Nature, 444, pp. 881-887
Van Gaal, L.F., Mertens, I.L., De Block, C.E., Mechanisms linking obesity with cardiovascular disease (2006) Nature, 444, pp. 875-880
Scheen, A.J., Current management strategies for coexisting diabetes mellitus and obesity (2003) Drugs, 63, pp. 1165-1184
Gaede, P., Vedel, P., Larsen, N., Jensen, G.V., Parving, H.H., Pedersen, O., Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes (2003) N Engl J Med, 348, pp. 383-393
Global guideline for type 2 diabetes: Recommendations for standard, comprehensive, and minimal care (2006) Diabet Med, 23, pp. 579-593. , IDF Clinical Guidelines Task force
Mikhailidis, D.P., Press, M., The importance of treating multiple cardiometabolic risk factors in patients with type 2 diabetes (2007) Expert Opin Pharmacother, 8, pp. 3009-3020
Scheen, A.J., Van Gaal, L.F., Després, J.-P., Pi-Sunyer, X., Golay, A., Hanotin, C., Le rimonabant améliore le profil de risque cardio-métabolique chez le sujet obèse ou en surpoids: Synthèse des études "RIO" (2006) Rev Med Suisse, 2, pp. 1916-1923
Curioni, C., Andre, C., Rimonabant for overweight or obesity (2006) Cochrane Database Syst Rev, 4, p. 4
Xie, S., Furjanic, M.A., Ferrara, J.J., McAndrew, N.R., Ardino, E.L., Ngondara, A., Bernstein, Y., Raffa, R.B., The endocannabinoid system and rimonabant: A new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism -or inverse agonism -as potential obesity treatment and other therapeutic use (2007) J.Clin Pharm Ther, 32, pp. 209-231
http://www.emea.europa.eu/humandocs/Humans/EPAR/acomplia/acomplia.htm, (accessed 16 January 2008)
Van Gaal, L.F., Rissanen, A.M., Scheen, A.J., Ziegler, O., Rössner, S., Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study (2005) Lancet, 365, pp. 1389-1397
Van Gaal, L.F., Scheen, A.J., Rissanen, A.M., Rössner, S., Hanotin, C., Ziegler, O., Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: 2-year results from the RIO-Europe Study (2008) Eur Heart J, 29. , (in press)
Pi-Sunyer, F.X., Aronne, L.J., Heshmati, H.M., Devin, J., Rosenstock, J., Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients. RIO-North America: A randomized controlled trial (2006) JAMA, 295, pp. 761-775. , and RIO-North America Study Group
Després, J.P., Golay, A., Sjöström, L., Effects on metabolic risk factors in overweight patients with dyslipidemia (2005) N Engl J Med, 353, pp. 2121-2134
Cote, M., Mauriege, P., Bergeron, J., Almeras, N., Tremblay, A., Lemieux, I., Després, J.P., Adiponectinemia in visceral obesity: Impact on glucose tolerance and plasma lipoprotein and lipid levels in men (2005) J.Clin Endocrinol Metab, 90, pp. 1434-1439
Guerre-Millo, M., Adiponectin: An update (2008) Diab Metab, 34, pp. 12-18
Després, J.P., Van Gaal, L., Scheen, A., Pi-Sunyer, X., Rimonabant improves cardiometabolic risk factors in overweight/obese patients irrespective of treatment with statins: Pooled data from the RIO program (Abstract) (2006) Atherosclerosis, 7 (SUPPL. 3), p. 329
Ruilope, L.M., Després, J.P., Scheen, A., Pi-Sunyer, X., Mancia, G., Zanchetti, A., Van Gaal, L., Effect of rimonabant on blood pressure in overweight/obese patients with/ without co-morbidities: Analysis of pooled Rimonabant In Obesity (RIO) study results (2008) J.Hypertens, 26, pp. 357-367
Pi-Sunyer, F.-X., Després, J.-P., Scheen, A., Van Gaal, L., Improvement of metabolic effects with rimonabant beyond the effect attributable to weight loss alone: Pooled one year data from the RIO (Rimonabant In Obesity and Related Metabolic Disorders) program (2006) JACC, 47 (SUPPL. A), pp. 362-A. , (Abstract)
Scheen, A.J., Finer, N., Hollander, P., Jensen, M.D., Van Gaal, L.F., Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: A randomised controlled study (2006) Lancet, 368, pp. 1660-1672. , for the RIO-Diabetes Study Group. diabetes:
Després, J.P., Van Gaal, L., Golay, A., Rissanen, A., Rimonabant improves oral glucose tolerance in non-diabetic overweight/ obese patients with/without comorbidities (2006) Diabetes, 55 (SUPPL. 1), pp. A80-A81. , (Abstract)
Scheen, A.J., The endocannabinoid system, a promising target for the management of type 2 diabetes (2008) Curr Protein Pept Sci, , in press
Scheen, A., Van Gaal, L., The CB1 blocker rimonabant reduces liver enzyme levels in overweight/ obese people with type 2 diabetes: The RIO Diabetes study (2006) Diabetic Med, 23 (SUPPL. 4), pp. 251-252. , (Abstract)
Osei-Hyiaman, D., DePetrillo, M., Pacher, P., Liu, J., Radaeva, S., Bátkai, S., Harvey-White, J., Kunos, G., Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity (2005) J.Clin Invest, 115, pp. 1298-1305
Luyckx, F.H., Scheen, A.J., Lefèbvre, P.J., Non-alcoholic steatohepatitis: Association with obesity and insulin resistance, and influence of weight loss (2000) Diabetes Metab, 26, pp. 98-106
Rosenstock, J., Iranmanesh, A., Hollander, P.A., Improved glycemic control with weight loss plus beneficial effects on atherogenic dyslipidemia with rimonabant in drug-naïve type 2 diabetes: The serenade trial (2007) Diabetes, 56 (SUPPL. 1), pp. A49-A50. , (Abstract)
Lafontan, M., Piazza, P.V., Girard, J., Effects of CB1 antagonist on the control of metabolic functions in obese type 2 diabetic patients (2007) Diabetes Metab, 33, pp. 85-95
Scheen, A.J., Cannabinoid-1 receptor antagonists in type-2 diabetes (2007) Best Pract Res Clin Endocrinol Metab, 21, pp. 535-553
Anderson, J.W., Kendall, C.W.C., Jenkins, D.J.A., Importance of weight management in type 2 diabetes: Review with meta-analysis of clinical studies (2003) J.Am Coll Nutr, 22, pp. 331-339
Joffe, D., Yanagisawa, R.T., Metabolic syndrome and type 2 diabetes: Can we stop the weight gain with diabetes (2007) Med Clin North Am, 91, pp. 1107-1123
Van Gaal, L.F., Pi-Sunyer, X., Després, J.P., Mc Carthy, C., Scheen, A.J., Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: Pooled 1-year data from the RIO program (2008) Diabetes Care, 31 (SUPPL. 2), pp. S229-S240
Christensen, R., Kristensen, P.K., Bartels, E.M., Bliddal, H., Astrup, A., Efficacy and safety of the weight-loss drug rimonabant: A meta-analysis of randomised trials (2007) Lancet, 370, pp. 1706-1713
Food and Drug Administration, , http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4306b1-00-index.htm
Serra, G., Fratta, W., A possible role for the endocannabinoid system in the neurobiology of depression (2007) Clin Pract Epidemiol Mental Health, 3, p. 25
Addy, C., Wright, H., Van Laere, K., Gantz, I., Erondu, N., Musser, B.J., Lu, K., Heymsfield, S.B., The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake (2008) Cell Metab, 7, pp. 68-78
Gadde, K.M., Allison, D.B., Cannabinoid-1 receptor antagonist, rimonabant, for management of obesity and related risks (2006) Circulation, 114, pp. 974-984
Gelfand, E.V., Cannon, C.P., Rimonabant: A cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors (2006) J.Am Coll Cardiol, 47, pp. 1919-1926
Bifulco, M., Grimaldi, C., Gazzerro, P., Pisanti, S., Santoro, A., Rimonabant: Just an antiobesity drug? Current evidence on its pleiotropic effects (2007) Mol Pharmacol, 71, pp. 1445-1456
Padwal, R.S., Majumdar, S.R., Drug treatments for obesity: Orlistat, sibutramine, and rimonabant (2007) Lancet, 369, pp. 71-77
Rucker, D., Padwal, R., Li, S.K., Curioni, C., Lau, D.C.W., Long term pharmacotherapy for obesity and overweight: Updated meta-analysis (2007) BMJ, 335, pp. 1194-1199
Bays, H., Blonde, L., Rosenson, R., Adiposopathy: How do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients? (2006) Expert Rev Cardiovasc Ther, 4, pp. 871-895
(2007) Summary of Product Characteristics, , http://www.emea.europa.eu/humandocs/PDFs/EPAR/acomplia/H-666-PI-en.pdf, Acomplia European Public Assessment Report. (accessed 21 November 2007)
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
