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Query: UMLS:C0497406 (overweight)
 26,365 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over past centuries, Cannabis sativa (Delta(9)-tetrahydrocannabinol being the principal active ingredient) has been used extensively for both medicinal and recreational uses, and one widely reported effect is the onset of a ravenous appetite and eating behaviour. The pharmacological properties of such exogenous cannabinoids are mediated through the activation of two receptor subtypes, the CB(1) and CB(2) receptors. A number of endogenous ligands for these receptors, the endocannabinoids, have now also been identified allowing their effects on ingestive behaviour to be determined. In a number of species, including man, the administration of exogenous and endogenous cannabinoids leads to robust increases in food intake and can promote body weight gain. These effects are believed to be mediated through activation of the CB(1) receptor. Conversely, experiments with selective CB(1) receptor antagonists have demonstrated reductions in food intake and body weight with repeated compound administration. These reductions in body weight appear to be greater in obese animals and may be the result of a dual effect on both food intake and metabolic processes. Such findings have led to a number of pharmaceutical companies developing selective CB(1) receptor antagonists for the treatment of obesity. The most advanced compound is Sanofi-Synthelabo's inverse agonist, rimonabant (Acomplia; SR-141716), and early Phase III results have recently demonstrated significant reductions in body weight, waist circumference and improvement of lipid and glucose metabolism in overweight and obese humans. Accordingly, the cannabinoid system appears to have an important role in the regulation of ingestive behaviour in man and animals.
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PMID:Cannabinoids and the regulation of ingestive behaviour. 1577 91

Development of the metabolic syndrome results from the interaction of genetic and environmental factors. Metabolic syndrome together with smoking represents risk factors for the development of cardiovascular complications. They may result from the hyperstimulation of the endocannabinoid system. The CB1 receptor has been assumed to play an important role in the endocannabionoid system. It is abundantly expressed in the brain, and in other parts of human body such as in the fat tissue. Rimonabant is a selective blocker of cannabinoid-1 (CB1) receptors and participates in the regulation of impaired endocannabinoid system. In the overweight humans, it stimulates sustained reduction of the body weight, girth size and it improves lipid and glucose metabolism. Rimonabant also reduces nicotine self-administration and may be effective not only as an aid for smoking cessation but also in the prevention of body weight increase related to the smoking cessation as it was documented in Rio-Lipids and Stratus-us studies.
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PMID:[Endocannabinoids--the new option in the treatment of metabolic syndrome and in smoking cessation]. 1580 91

Rimonabant hydrochloride, the first drug in a new class of selective cannabinoid type 1 (CB1) receptor antagonists, is showing promise in clinical trials for the treatment of obesity and related metabolic risk factors, in addition to tobacco dependence. Results of phase III clinical trials comparing rimonabant with placebo found that overweight or obese patients, with or without untreated dyslipidemia or type 2 diabetes, lost significant body weight when treated with rimonabant 20 mg for a year. The weight loss was accompanied by a decrease in waist circumference, demonstrating a significant reduction in abdominal obesity, which is an independent marker for cardiovascular disease. Significant improvements were also observed in the lipid profile, with an increase in high-density lipoprotein (HDL) cholesterol and a decrease in triglyceride levels. Improvements in glucose tolerance and insulin levels were also found. Moreover, the number of patients diagnosed with the metabolic syndrome at baseline was significantly reduced. These beneficial effects of rimonabant 20 mg were maintained after 2 years of chronic treatment. Other phase III trials have shown that rimonabant helps people to quit smoking without significant post-cessation weight gain. Rimonabant has a favorable safety profile and is generally well tolerated. Rimonabant is proving to be a very promising approach for managing two major and preventable risk factors for cardiovascular disease. This review summarizes the available evidence on the clinical efficacy and safety of rimonabant as a potential therapy for obesity and smoking cessation.
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PMID:Rimonabant hydrochloride: an investigational agent for the management of cardiovascular risk factors. 1623 73

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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PMID:New approaches for the management of patients with multiple cardiometabolic risk factors. 1675 12

RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or overweight patients with or without comorbidities (RIO-Europe and RIO-North America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant.
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PMID:[Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: overview of RIO studies]. 1697 42

Rimonabant (SR141716, Acomplia) has been described as an antagonist/inverse agonist at the cannabinoid receptor type 1 (CB1). It has been widely used as a tool to evaluate the mechanisms by which cannabinoid agonists produce their pharmacological effects and to elucidate the respective physiological or pathophysiological roles of the CB1 receptor. It has become increasingly clear that rimonabant can exert its own intrinsic actions. These may be viewed as evidence of either the inverse agonist nature of rimonabant or of tonic activity of the endocannabinoid system. To date, data obtained from clinical trials (RIO North America, RIO Europe and RIO Lipid) indicate that rimonabant may have clinical benefits in relation to its anti-obesity properties and as a novel candidate for the treatment of metabolic and cardiovascular disorders associated with overweight and obesity. Other clinical trials, such as the STRATUS study, have also shown that rimonabant may be effective in smoking cessation, and that the drug has a reasonable safety profile. Recently, it has been shown that rimonabant prevents indomethacin-induced intestinal injury by decreasing the levels of pro-inflammatory cytokine tumour necrosis factor alpha (TNFalpha), thus indicating that CB1 receptor antagonists might exhibit potential anti-inflammatory activity in acute and chronic diseases.
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PMID:Therapeutic potential of targeting the endocannabinoids: implications for the treatment of obesity, metabolic syndrome, drug abuse and smoking cessation. 1701 18

Obesity and being overweight are risk factors for kidney diseases. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 ml/min/1.73 m(2)) is related to the increasing number of components of the metabolic syndrome; that is, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol level and hypertension. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise) or eventually by antiobesity medication or bariatric surgery. Rimonabant, a new antiobesity medication, showed beneficial potential effect in treating clusters of metabolic syndrome, which may ultimately suggest potential benefit in treating obesity-related glomerulopathy.
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PMID:Rimonabant as a potential new treatment for an emerging epidemic of obesity-related glomerulopathy? 1706 18

Rimonabant is the first of a new class of selective cannabinoid receptor-1 blockers. It reduces the overactivity of the endocannabinoid system, improving lipid and glucose metabolism and regulating food intake and energy balance. In four randomised, double-blind clinical trials in overweight or obese adults with or without type 2 diabetes and/or dyslipidaemia, oral rimonabant 20mg once daily reduced weight and waist circumference to a significantly greater extent than placebo. A significantly greater proportion of rimonabant than placebo recipients achieved the clinically significant weight-loss target of > or =5% or > or =10% of initial weight. Rimonabant was associated with significant improvements in glycaemic control relative to placebo, with approximately equal to 57% of the reduction in glycosylated haemoglobin being independent of the effects of weight loss in one trial. Improvements in other cardiometabolic risk factors (i.e. increases in high-density lipoprotein-cholesterol [HDL-C] and decreases in triglyceride [TG] levels) were significantly greater with rimonabant than with placebo. The improvement in lipid profile also demonstrated a weight-independent effect, with approximately equal to 47-58% of the improvement in HDL-C and TG being beyond that expected through weight loss alone. Rimonabant was generally well tolerated, with most adverse events considered mild to moderate in severity.
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PMID:Rimonabant. 1711 4

Rimonabant significantly reduces weight and waist circumference and improves dyslipidemias in overweight and obese patients without diabetes mellitus. Numerous other metabolic changes, including reduced prevalence of the metabolic syndrome and associated cardiovascular disease (CVD) risk factors, reduced fasting glucose, and elevated adiponectin, have been demonstrated with the administration of rimonabant. The Rimonabant-in-Obesity (RIO)-Diabetes trial studied the safety and efficacy of rimonabant in overweight and obese patients with type 2 diabetes who were treated with metformin or sulfonylureas. RIO-Diabetes was a 1-year, randomized, double-blind, placebo-controlled, parallel-group study of 1,047 overweight/obese patients with type 2 diabetes in 151 centers in 11 countries. The body mass index of participants ranged from 27 to 40. Glycosylated hemoglobin (HbA1c) at screening ranged from 6.5% to 10.0%. All patients were receiving either metformin or sulfonylurea therapy and were asked to follow a hypocaloric diet (600 kcal/day deficit [1 kcal = 4.2 kJ]) for the duration of the trial. After a 4-week placebo plus diet run-in period, patients were randomized to receive placebo or rimonabant 5 mg or 20 mg once daily. At 1 year, absolute change in weight from baseline in the intention-to-treat, last observation carried forward analysis of the rimonabant 5 mg and 20 mg groups, respectively, was loss of 2.3 kg and 5.3 kg compared with 1.4 kg in the placebo group (P = 0.013 and P <0.001, respectively). Waist circumference was significantly decreased in the rimonabant 5-mg and 20-mg groups by 2.9 cm and 5.2 cm compared with 1.9 cm in the placebo group (P = 0.034 and P <0.001, respectively). HbA1c reductions of 0.1% and 0.6% were significant in the rimonabant 5-mg and 20-mg groups (P = 0.034 and P <0.001, respectively). Some 57% of the improvements in HbA(1c) and high-density lipoprotein cholesterol could not be attributed to observed weight loss. Compared with placebo, rimonabant 20 mg also demonstrated significant improvements in the prevalence of metabolic syndrome and improvement in its constituents, as well as systolic blood pressure and C-reactive protein levels (assay by ICON Laboratories, Farmingdale, NY and Dublin, Ireland). Rimonabant is the first selective cannabinoid1 blocker studied for type 2 diabetes and associated CVD risk factor therapy. Its ability to improve the numerous metabolic pathologies associated with diabetes and CVD risk and concomitantly to reduce weight and waist circumference introduces a strongly positive new dynamic in type 2 diabetes treatment. Its multifactorial mechanisms warrant further investigation and may provide insights into other pathologies.
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PMID:Endocannabinoid blockade for improving glycemic control and lipids in patients with type 2 diabetes mellitus. 1729 41

Rimonabant (Acomplia) is the first selective CB1 receptor blocker of the endocannabinoid system. It has been evaluated in the RIO ("Rimonabant In Obesity and related disorders") programme including above 6.600 overweight/obese patients with or without comorbidities followed for 1 to 2 years. Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. In patients with type 2 diabetes, rimonabant also diminishes HbA1c levels, an effect confirmed in the recent SERENADE trial. Almost half of the metabolic effects occurs beyond weight loss, suggesting direct peripheral effects of rimonabant. Rimonabant is indicated in Europe as an adjunct to diet and exercise for the treatment of obese patients, or overweight patients with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.
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PMID:[Cardiometabolic effects of rimonabant in obese/overweight subjects with dyslipidaemia or type 2 diabetes]. 1746 Dec 96


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