Randomized, double-blind trial of chitosan for body weight reduction. [Effect of chitosan in complex management of obesity]. The effect of the dietary supplement, Chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults. Evaluating efficacy of a chitosan product using a double-blinded, placebo-controlled protocol. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor.
Overweight and obesity is a prevalent and costly threat to public health. Compelling evidence links overweight and obesity with serious disorders such as cardiovascular diseases and diabetes. Dietary regimen are notoriously burdened with poor compliance. Chitosan is promoted in the US and other countries as an oral remedy to reduce fat absorption and has now been incorporated as a major constituent into several over-the-counter remedies. The primary aim of this study is to investigate the clinical effectiveness of oral chitosan for body weight reduction.
                Thirty-four overweight volunteers were included in a randomized placebo-controlled double-blind trial. Subjects were assigned to receive either four capsules of chitosan or indistinguishable placebo twice daily for 28 consecutive days. Measurements were taken at baseline, after 14 and 28d of treatment. Subjects maintained their normal diet and documented the type and amount of food consumed. Adverse effects were assessed and compliance monitored.
                Data from 30 subjects were entered into an intention-to-treat analysis. After four weeks of treatment, body mass index, serum cholesterol, triglycerides, vitamin A, D, E and beta-carotene were not significantly different in subjects receiving chitosan compared to those receiving placebo. Vitamin K was significantly increased after four weeks in the chitosan group compared with placebo (P<0.05). Compliance was 91.5% and 96.0% for chitosan and placebo groups respectively.
                The above data suggest that chitosan in the administered dosage, without dietary alterations, does not reduce body weight in overweight subjects. No serious adverse effects were reported. The aim of the present study was to verify the effect of chitosan as a possible adjuvant in the complex management of obesity.
                Fifty obese women (22-59 years, BMI > 30) participated in the study. A six months program consisted of 2-hour meetings with a physician, psychologist and dietitian, in a group of about 20 persons, every two weeks. Low calorie diet (1000 kcal/day), physical activity and behaviour modification were recommended. Supplementation with chitosan was evaluated in a randomized, placebo-controlled, double-blind study. In the chitosan group, participants received ChitininN (Primex Ingredients ASA, Avaldsnes, Norway) i.e. 750 mg pure chitosan per tablet, two tablets three times daily before each main meal. The placebo group received identical placebo tablets.
                Significantly higher body weight loss was noted in the chitosan-supplemented group (15.9 kg) than in the placebo group (10.9 kg) Also a greater decrease of systolic and diastolic blood pressure was observed in the chitosan group. There was no difference between the groups in the decrease of LDL and total cholesterol. No adverse effects were noted but the number of drop-outs was higher in the placebo group than in the chitosan group.
                Chitosan can be used as a valuable and safe adjuvant in long-term dietary treatment of obesity. Chitosan seems to accentuate the reduction of blood pressure associated with weight reduction. Chitosan, a deacetylated chitin, is a widely available dietary supplement purported to decrease body weight and serum lipids through gastrointestinal fat binding. Although evaluated in a number of trials, its efficacy remains in dispute.
                To evaluate the efficacy of chitosan for weight loss in overweight and obese adults.
                A 24-week randomised, double-blind, placebo-controlled trial, conducted at the University of Auckland between November 2001 and December 2002.
                A total of 250 participants (82% women; mean (s.d.) body mass index, 35.5 (5.1) kg/m(2); mean age, 48 (12) y)
                Participants were randomly assigned to receive 3 g chitosan/day (n=125) or placebo (n=125). All participants received standardised dietary and lifestyle advice for weight loss. Adherence was monitored by capsule counts.
                The primary outcome measure was change in body weight. Secondary outcomes included changes in body mass index, waist circumference, body fat percentage, blood pressure, serum lipids, plasma glucose, fat-soluble vitamins, faecal fat, and health-related quality of life.
                In an intention-to-treat analysis with the last observation carried forward, the chitosan group lost more body weight than the placebo group (mean (s.e.), -0.4 (0.2) kg (0.4% loss) vs +0.2 (0.2) kg (0.2% gain), P=0.03) during the 24-week intervention, but effects were small. Similar small changes occurred in circulating total and LDL cholesterol, and glucose (P<0.01). There were no significant differences between groups for any of the other measured outcomes.
                In this 24-week trial, chitosan treatment did not result in a clinically significant loss of body weight compared with placebo. To examine the safety and efficacy of a chitosan dietary supplement on body composition under free-living conditions.
                In a randomized, double-blinded, placebo-controlled dietary intervention protocol, subjects were assigned to a treatment group (TRT), a placebo group (PLA) and a control group (CTL).
                A total of 150 overweight adults enrolled; 134 (89.3%) completed the study; 111 (82.8%) were women who were similarly distributed in the three groups.
                The TRT group took six 500 mg chitosan capsules per day and both TRT and PLA groups wore pedometers during their waking hours and recorded daily step totals. The CTL group followed weight loss programs of their choice, and took the same baseline and ending tests.
                Outcome measures were Dual Energy X-ray Absorptiometry tests, fasting blood chemistries, and self-reported daily activity levels and caloric intakes.
                Compared to CTL, the TRT group lost more weight (-2.8 lbs vs. +0.8 lbs, p < 0.001) and fat mass (-2.6 lbs vs. +0.1 lbs, p = 0.006). Compared to PLA, the TRT group lost more weight (-2.8 lbs. vs. -0.6 lbs, p = 0.03), % fat (-0.8% vs. +0.4%, p = 0.003), fat mass (-2.6 lbs vs. +0.6 lbs, p = 0.001) and had a greater body composition improvement index (BCI) (+2.4 lbs vs. -1.9 lbs, p = 0.002).
                These data provide evidence for the efficacy of a chitosan compound to facilitate the depletion of excess body fat under free-living conditions with minimal loss of fat-free or lean body mass. 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. It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients.
                In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat.
                Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001).
                Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction]. Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits.
                Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo.
                In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01).
                Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year. The researchers assessed the long-term weight reduction efficacy, tolerability, and safety of sibutramine used once daily in conjunction with behavior modification to treat mild to moderate obesity.
                This was a double-blind randomized placebo-controlled parallel-group comparative study of sibutramine 10 mg or 15 mg (or placebo) once daily for 1 year, given with dietary advice.
                A total of 485 obese men and women with uncomplicated obesity were included (mean age=42 years, mean body mass index=32.7 kg/m2).
                The outcomes were mean weight loss, percentage losing more than 5% or 10% of their body weight, and adverse drug effects.
                Among patients completing the study, those taking sibutramine 10 mg or 15 mg had greater mean weight loss compared with placebo at 12-month assessment (P < or = .001). Changes in body weight from baseline to end point were -1.6 kg for those taking placebo, -4.4 kg for those taking sibutramine 10 mg (P < or =.01, last observation carried forward [LOCF]), and -6.4 kg for those taking sibutramine 15 mg (P < or =.001, LOCF). For placebo patients, 20% lost 5% or more of their body weight compared with 39% of patients taking sibutramine 10 mg and 57% taking sibutramine 15 mg. Only 7% of the patients taking placebo lost 10% or more of their body weight, compared with 19% taking sibutramine 10 mg and 34% taking sibutramine 15 mg (P <.001 for both 10 mg and 15 mg vs placebo, and for both > or =5% and > or =10%).
                Sibutramine 10 mg or 15 mg once daily given with dietary advice produces and maintains statistically and clinically significantly greater weight loss than dietary advice alone (placebo) throughout a 12-month treatment period, and is safe and well tolerated. To assess the efficacy and tolerability of orlistat (Xenical) in producing and maintaining weight loss over a 12-month period.
                Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months.
                Five centres in the UK.
                228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg (range 74-144 kg).
                All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy deficit of approximately 600 kcal/day, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily.
                Change in body weight (the primary efficacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and beta carotene.
                Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P < 0.05), and 28% and 17%, respectively (P = 0.04) lost at least 10% of body weight. Orlistat-treated patients showed significant decreases (P < 0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein: high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event profiles, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistat-treated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and beta carotene was significantly greater in orlistat-treated patients compared with those receiving placebo (P < 0.001). No significant change was found in the mean vitamin E:total cholesterol ratio in either group after 52 weeks.
                Orlistat, in conjunction with a low-energy diet, produced greater and more frequent significant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss (> or = 5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.
There is some evidence that chitosan is more effective than placebo in the short-term treatment of overweight and obesity. However, many trials to date have been of poor quality and results have been variable. Results obtained from high quality trials indicate that the effect of chitosan on body weight is minimal and unlikely to be of clinical significance.