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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. Lancet 368, 1660-1672

University of Cambridge, Cambridge, England, United Kingdom
The Lancet (Impact Factor: 45.22). 12/2006; 368(9548):1660-72. DOI: 10.1016/S0140-6736(06)69571-8
Source: PubMed

ABSTRACT Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas.
1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00029848.
692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 vs placebo). Rimonabant was generally well tolerated. The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group, mainly due to depressed mood disorders, nausea, and dizziness.
These data indicate that 20 mg/day rimonabant, in combination with diet and exercise, can produce a clinically meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas.

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    • "The pathophysiology of type 2 diabetes is closely related to these disorders. Clinical studies investigated that, treatment of overweight type 2 diabetic patients with rimonabant (CB1 antagonism) (20 mg/day for 1year) significantly reduced body weight and improved glycemic control and HbA1C levels in comparison to placebo (Scheen et al., 2006). The aim of this study was to determine whether G1359A polymorphism of CNR1 is associated with coronary artery disease (CAD) with and without type 2 diabetes mellitus (T2DM) and with T2DM patients free of CAD and to elucidate the association of G1359A polymorphism of CNR1 with lipid profile and other cardiovascular risk factors. "
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    ABSTRACT: Emerging evidence that the cannabinoid type 1 receptor (CB1) and its endogenous ligands, endocannabinoids, involved in regulation of feeding behavior and body weight. Over-activation of ECS is associated with metabolic diseases as dyslipidemia and insulin resistance involved in CAD and diabetes. The aim was to determine whether G1359A polymorphism of CNR1 associated with CAD with and without T2DM, and with T2DM patients free of CAD and elucidate the association of CNR1 polymorphism with CAD risk factors. The study was carried on 50 patients with CAD (25 patients with and 25 patients without T2DM), 25 patients with T2DM free of CAD and a group of 20 healthy subjects as a control group. Coronary artery angiography for patient group, serum lipid profile (TG, TC, LDL and HDL) and assessment of G1359A polymorphism of CNR1 by RFLP method were done. CAD patients with and without T2DM had significantly higher age, fasting blood glucose, systolic and diastolic blood pressure, male gender, smoking, and body mass index (BMI) compared with control. GG genotype and G allele of G1359A polymorphism were significantly associated with CAD patients with T2DM (p<0.05). G allele increased risk of occurrence of CAD with diabetes by 5.22 (OR) 95% CI (1.32-20.54). GG genotype was significantly associated with higher TC (p<0.01), LDLc (p<0.001) and BMI (p=0.001). Association of G1359A polymorphism with BMI and disordered lipid may explain in part its association with CAD patients with T2DM and may encourage use of cannabinoid receptor antagonist in treatment of these disorders. Copyright © 2013 Safaa I. Tayel, et al., This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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    • "In addition to obesity, CB 1 antagonists have been in particular proposed as therapeutic agents for smoking cessation [16], drug abuse [24e26], liver fibrosis [27], obesity-associated hepatic steatosis [28], sexual dysfunction [29], metabolic syndrome and dyslipidemia [30]. Cardiovascular and metabolic risk factor improvements due to the administration of CB 1 antagonists have been also highlighted in type 2 diabetes patients [31]. Despite initial enthusiasm in drug discovery for the identification and the selection of first CB 1 antagonist candidates able to reach the pharmaceutical market, with reference to the well known history "
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    • "Cannabinoid CB1 receptor antagonists and inverse agonists, such as rimonabant, AM 4113, and AM251 (e.g., [23] [24] [25]) have drawn attention as drugs that can be used to treat behavioral disorders involved with overeating, such as obesity, by reducing food intake (see [26] [27] for reviews). Rimonabant is probably the most well researched of these drugs to date, and indeed has been shown to reduce free food intake in animal studies [28] [29] [30] [31] [32] [33] [34] [35] [36] [37], as well as reduce weight in clinical trials studies with obese humans [38] [39] [40] [41] [42] [43]. Though rimonabant has side effects that have called into question its application for weight loss [44] [45], the cannabinoid drug class is still of interest in treating disorders in which excessive contact with a reinforcing stimulus, such as food or drugs, is relevant [26,45–48]. "
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