CB1 receptor blockade and its impact on cardiometabolic risk factors: overview of the RIO programme with rimonabant.
Open accessAbstract
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.
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Psychiatric side effects associated with CB1 antagonists/inverse agonists, such as depression- and anxiety-like states, have been reported, leading patients to drop out and discontinue treatment.
“psychiatric side effects associated with CB1 antagonists/inverse agonists, such as depression- and anxiety-like states, have been reported in several studies, leading patients to drop out of studies and discontinue treatment 63– 65.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [64]
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Psychosocial and pharmacological interventions for the treatment of cannabis use disorder
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- Authors
- Scheen, A. J.
- Affiliations
- University of Liège (BE)
- Corresponding author
- Scheen, A. J.
- ORCID
- Scheen, A. J.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2008-04-17
- Volume
- 20
- Issue
- s1
- Pages
- 139-146
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W1994145229
- Cited by
- 68
- References
- 47
- Citations by year
- 2025: 2 · 2023: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 5
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Keywords
- rimonabant, CB1 receptor antagonism, obesity, type 2 diabetes, cardiometabolic risk factors, weight loss, insulin resistance, dyslipidemia, HDL cholesterol, adiponectin, small dense LDL, HbA1c, C-reactive protein, antidepressant safety
- MeSH terms
- Rimonabant, Algorithms, Cardiovascular Diseases, Clinical Trials as Topic, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Obesity, Piperidines, Pyrazoles, Risk Factors, Treatment Outcome, Anti-Obesity Agents, Metabolic Syndrome, Receptor, Cannabinoid, CB1
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