Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity.

OBJECTIVE: 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. STUDY DESIGN: 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. POPULATION: 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). OUTCOMES MEASURED: The outcomes were mean weight loss, percentage losing more than 5% or 10% of their body weight, and adverse drug effects. RESULTS: 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%). CONCLUSIONS: 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.     

Orlistat in the long-term treatment of obesity in primary care settings

OBJECTIVE: To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. PARTICIPANTS: A group of 796 obese patients (body mass index, 30-44 kg/m2), treated with placebo 3 times a day (TID), 60 mg of orlistat TID, or 120 mg of orlistat TID, in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year. SETTING: Seventeen primary care centers in the United States. MAIN OUTCOME MEASURES: Changes in body weight and obesity-related disease risk factors. RESULTS: Patients treated with orlistat lost significantly more weight (7.08 +/- 0.54 and 7.94 +/- 0.57 kg for the 60-mg and 120-mg orlistat groups, respectively) than those treated with placebo (4.14 +/- 0.56 kg) in year 1 (P<.001) and sustained more of this weight loss during year 2 (P<.001). More patients treated with orlistat lost 5% or more of their initial weight in year 1 (48.8% and 50.5% of patients in the 60-mg and 120-mg groups, respectively) compared with placebo (30.7%; P<.001), and approximately 34% of patients in the orlistat groups sustained weight loss of 5% or greater over 2 years compared with 24% in the placebo group (P<.001). Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated, although treatment resulted in a higher incidence of gastrointestinal events. CONCLUSIONS: This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care settings.     

Cost-effectiveness of sibutramine in the treatment of obesity.

BACKGROUND: This study reports incremental cost-utility of sibutramine compared to diet and lifestyle advice for the treatment of obesity. METHOD: The model estimates the costs and quality of life benefits associated with weight loss itself and the reduced incidence of coronary heart disease (CHD) and diabetes in the "healthy obese." The key source of effectiveness data is 2 randomized controlled trials over 12 months. Utility gain per kilogram lost is analyzed using Short Form-36 data from sibutramine trials. The impact on CHD is estimated using the Framingham risk equation, which relates age/sex/body mass index to risk of heart disease. The reduced incidence of diabetes due to weight loss is estimated from published literature. A life tables approach was used to calculate the cost per quality-adjusted life year (QALY) of 1 year's treatment with sibutramine compared to diet and lifestyle advice. RESULTS: The incremental cost per QALY of sibutramine is 4,780 UK pounds. Sensitivity analyses show that this result is sensitive to utility associated with weight loss and the frequency of monitoring. CONCLUSIONS: Sibutramine is a cost-effective treatment for obesity when combined with diet and lifestyle advice.     

Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study.

BACKGROUND: Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment. OBJECTIVE: This multicenter, double-blind, placebo-controlled study was designed to test the hypothesis that orlistat, a gastrointestinal lipase inhibitor, is significantly more effective than a placebo in preventing weight regain. DESIGN: Obese subjects who lost > or = 8% of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (4180-kJ/d deficit) with no adjunctive pharmacotherapy were randomly assigned to receive placebo, 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 times daily for 1 y in combination with a maintenance diet to help prevent weight regain. Of 1313 recruited subjects [body mass index (in kg/m2): 28-43], 729 subjects lost > or =8% of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase. RESULTS: After 1 y, subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects (32.8 +/- 4.5% compared with 58.7 +/- 5.8% regain of lost weight; P < 0.001). Moreover, more subjects in the 120-mg orlistat group than in the placebo group regained < or = 25% of lost weight (47.5% of subjects compared with 29.9%). In addition, orlistat treatment (120 mg 3 times daily) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo (P < 0.001). CONCLUSION: The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors.     

A randomized double-blind crossover study of the antiobesity effects of etiocholanedione

Etiocholanedione (ED), a natural metabolite of dehydroepiandrosterone, has antiobesity effects in animals when given orally and is nontoxic. We carried out a trial of oral ED in obese humans. In a 20-week randomized double-blind crossover study, 14 subjects lost significantly more weight and body fat during treatment with oral ED, 4 gm daily, than during placebo administration. Mean weight loss during ED administration was 2.8 +/- 5.5 kilograms, which was equivalent to 0.53 +/- 0.91 kilograms per week per 100 kilograms of body fat; mean weight change during placebo administration was essentially zero: +0.21 +/- 4.2 kg, or +0.04 +/- 0.74 kg/wk/100 kg body fat. The difference between the weight changes in the two periods was significant: for delta kg, P < 0.05; for delta kg/wk/100 kg body fat, P < 0.03. Densitometric measurement of body fat content showed that the mean weight loss coincided almost exactly with the mean decrease in fat content; thus, over the 10-week period of ED administration, the mean fat loss was about 5% of the initial body fat content. Three of the obese subjects had strikingly greater fat loss, about 18%, 19%, and 25% of the initial body fat content. There were no significant subjective or objective side effects of ED administration.     

Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials

OBJECTIVE: Sibutramine causes weight loss by suppressing the appetite and by promoting energy expenditure, but it can also increase blood pressure through a norepinephrine effect. The aim of this study was to provide a comprehensive meta-analysis of randomized, controlled trials on the effects of sibutramine on blood pressure and weight loss. RESEARCH METHODS AND PROCEDURES: Twenty-one placebo-controlled, double-blind, randomized trials of sibutramine were identified using MEDLINE, EMBASE, and a manual search. The effect sizes of sibutramine on weight and systolic (SBP) and diastolic (DBP) blood pressure changes were estimated. Subgroup analyses were undertaken to explore the relationship between effect sizes and the study characteristics. RESULTS: The effect size of sibutramine on weight change was -1.00 (-1.17 to -0.84), whereas the effect sizes on SBP and DBP changes were 0.16 (0.08 to 0.24) and 0.26 (0.18 to 0.33), respectively. By subgroup analysis, the effect sizes on weight loss were significantly larger when the dosage was > or = 15 mg. The effect sizes on increased SBP were significantly larger when the initial body weight was > or = 92 kg and the age was < 44 years; similarly, the effect sizes on increased DBP were significantly larger when the initial weight was > or = 92 kg. DISCUSSION: Sibutramine showed a large effect on weight loss. Because blood pressure was found to be increased slightly, but significantly, sibutramine should be used cautiously in patients with borderline or high blood pressure. Additional studies on its effect on blood pressure are needed.     

Weight changes after vertical banded gastroplication

AIMS: This study assessed the patterns of weight change in response to surgical treatment for obesity. METHODS: Vertical Banded Gastroplication (VBG) was performed during the period 1994-2000. Patients were required to follow a liquid diet (800 kcals)for 12 weeks before surgery. The same diet plus a multivitamin capsule (Forceval) was followed for 12 weeks postoperatively, after which normal foods were introduced. Data from 23 patients, 16 women and 7 men, aged 33-63 years (mean, SD; 42 +/- 8 yrs), with BMI from 38 to 69 kg/m2 (52.5 +/- 8.1 kg/m2) at the time of the surgery were available for analysis. Follow up was 3 to 7 years (mean 4 years). RESULTS: An initial weight loss of 44.4 +/- 24.3 kg (min 11.5, max 110.5 kg) was reached during the first two years (mean BMI decrease 15.8 kg/m2). However a regain in weight (36% of the initial weight loss = 5.6 kg/m2) up to 3 to 7 years after surgery was usual. Average annual regain was 13.6 kg (n=17), 9.45 kg (n=11) and 0.8 kg (n=8) during the 3rd, 4th and 5th year after surgery). Five participants reached a BMI below 30 but only one, BMI < 25, has maintained all the weight loss after 5years. CONCLUSIONS: Weight lossfollowing VBG ceased after twoyears with a subsequent substantial weight regain. Auxiliary therapies to counteract weight regain are necessary after VBG.     

盐酸西布曲明治疗单纯性肥胖的对照研究

目的评价盐酸西布曲明治疗单纯性肥胖患者的有效性和安全性.方法采用多中心、随机、双盲、安慰剂平行对照的研究方法.选择年龄18～65岁,体质指数(BMI)27～40的单纯性肥胖患者.口服盐酸西布曲明10mg/d或安慰剂1粒/d,24周.观察体重变化及临床和常规实验室检查结果以评价药物的疗效和安全性.结果有效病例233例,其中对照组113例,治疗组120例.从第4周起盐酸西布曲明组体重降低值即大于安慰剂组,至24周盐酸西布曲明组平均体重降低值为(6.8±3.1)kg,安慰剂组为(0.48±2.6)kg.治疗组不良反应的发生率高于安慰剂组,但症状轻微,易于耐受.结论盐酸西布曲明10mg/d,治疗单纯性肥胖是有效和安全的.     

Combining behavioral and pharmacological treatments for obesity

Weight-loss medications are currently recommended for use only as an adjunct to diet, exercise, and behavior modification. Little, however, is known about the benefits of combining behavioral and pharmacological therapies or about the mechanisms that would make these combined approaches more effective than either used alone. This article reviews the effects of adding pharmacotherapy (i.e., principally sibutramine and orlistat) to a modest program of lifestyle modification. Studies revealed that the addition of medication typically improved short- and long-term weight loss compared with lifestyle modification alone. The best results, however, were obtained when medications were combined with an intensive, group program of lifestyle modification. The two approaches may have additive effects; behavioral treatment seems to help obese individuals control the external (i.e., food-related) environment, whereas pharmacotherapy may control the internal environment by reducing hunger, cravings, or nutrient absorption. The article examines possible methods of sequencing behavioral and pharmacological therapies and offers suggestions for future research.     

What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy,exercise, behaviour therapy or combinations of these interventions

BACKGROUND: Evidence is needed for the effectiveness of interventions given with reducing diets for obese adults: drug therapy, exercise, or behaviour therapy. METHODS: We systematically reviewed randomized controlled trials in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted data and a second checked data extraction. Trial quality was assessed. RESULTS: Adding orlistat to diet was associated with weight change for up to 24 months (-3.26 kg, 95% CI, -4.15 to -2.37 kg), and statistically significant beneficial changes were found for total and LDL cholesterol, blood pressure and glycaemic control. Adding sibutramine to diet was associated with a 12 month weight change of -4.18 kg (95% CI, -5.14 to -3.21 kg), and statistically significant beneficial effects on high density lipoprotein cholesterol (HDL) and triglycerides (TGs), but an increase in diastolic blood pressure. Adding exercise to diet, or to diet and behaviour therapy, was associated with improved weight loss for up to 36 months and improvements in HDL, TGs and blood pressure. Adding behaviour therapy to diet, or to diet and sibutramine together, was associated with improved weight loss for up to 18 months. Adding drugs, exercise or behaviour therapy to dietary advice was each associated with similar weight change. CONCLUSIONS: Adding orlistat, sibutramine, exercise, or behaviour modification to dietary advice can improve long-term weight loss.     

Sibutramine treatment in obesity: predictors of weight loss including rorschach personality data

OBJECTIVE: To study personality and clinical factors in weight loss by sibutramine (Meridia and Reductil), an anti-obesity drug enhancing satiety. RESEARCH METHODS AND PROCEDURES: The subjects were 30 obese patients [43 +/- 12 years (mean +/- SD), BMI 40 +/- 4 kg/m(2)]. The treatment comprised 15 mg of sibutramine administered daily and monthly dietary advice. Weight loss after 6 months of treatment was evaluated. For psychological assessment, the Rorschach method (Comprehensive System) and the Beck Depression Inventory were used. RESULTS: A multiple linear regression model including the Rorschach predictors' physical demand states (animal movement, designated as FM) being intrusive or difficult to hold and a dependency orientation (food contents) could explain 47% of 6 months of weight loss. A model including initial weight loss in addition to the Rorschach predictors explained 58% of the 6-month weight loss. DISCUSSION: The personality factors predicted greater weight loss. In particular, patients with difficulties concerning physical demand states, which would include hunger, could have reduced their eating behavior with enhanced satiety, resulting in greater weight loss. Enhanced satiety could also have helped patients with a dependent need for food to limit food intake. Being enrolled in a treatment program could also have provided essential support for patients with dependency needs. Furthermore, initial weight loss was a predictor of greater weight loss in sibutramine treatment, in accordance with prior research.     

Influence of sibutramine on energy expenditure in African American women

OBJECTIVE: African American women have a high prevalence of obesity, which partially may be explained by their lower rates of resting energy expenditure (REE). The aim of this study was to examine the influence of acute sibutramine administration on REE and post-exercise energy expenditure in African American women. RESEARCH METHODS AND PROCEDURES: A total of 15 premenopausal, African American women (age, 29 +/- 5 years; body fat, 38 +/- 7%) completed a randomized, double-blind cross-over design with a 30-mg ingestion of sibutramine or a placebo. Each trial was completed a month apart in the follicular phase and included a 30-minute measurement of REE 2.5 hours after sibutramine or placebo administration. This was followed by 40 minutes of cycling at approximately 70% of peak aerobic capacity and a subsequent 2-hour measurement of post-cycling energy expenditure. RESULTS: There was no difference (p > 0.05) in REE (23.70 +/- 2.81 vs. 23.69 +/- 2.95 kcal/30 min), exercise oxygen consumption (1.22 +/- 0.15 vs. 1.25 +/- 0.15 liter/min), and post-cycling energy expenditure (104.2 +/- 12.7 vs. 104.9 +/- 11.4 kcal/120 min) between the sibutramine and placebo trials, respectively. Cycling heart rate was significantly higher (p = 0.01) during the sibutramine (158 +/- 14 beats/min) vs. placebo (150 +/- 12 beats/min) trials. DISCUSSION: These data demonstrate that acute sibutramine ingestion does not increase REE or post-exercise energy expenditures but does increase exercising heart rate in overweight African American women. Sibutramine may, therefore, impact weight loss through energy intake and not energy expenditure mechanisms.     

Assessment of clinical and economic benefits of weight management with sibutramine in general practice in Germany

Obesity is associated with major health risks and a high economic burden impacting on health care systems. This study utilises the latest evidence from randomised clinical trials (RCTs) to explore and to assess the cost effectiveness of sibutramine in combination with diet and lifestyle advice compared to diet and lifestyle advice alone for the treatment of obese subjects without comorbidities at baseline in Germany. New evidence from recently published RCTs and post-marketing surveillance studies, including health economic data as well as quality of life (QoL) data, were used to model the long-term outcomes of weight management with sibutramine in German practice. German healthcare costs and new data from over 8,000 patients were analysed based on a recently published model. These new RCT data were used to model weight losses, proportion of responders to treatment, utilities by weight loss and variability in weight regain post-treatment. Costs and QoL benefits associated with weight loss (using SF-36 data from sibutramine trials), reduced incidence of coronary heart disease (using Framingham equations) and diabetes were used to estimate the cost per quality adjusted life year of sibutramine treatment. For 1,000 patients treated with sibutramine for 1 year, extrapolating outcomes over 4 further years, sibutramine is estimated to save 4.18 CHD events, 2.58 diabetes incident cases and give 51.5 more quality-adjusted life years (QALYs). The cost-utility analysis (CUA) estimates €13,706 per QALY gained. Results are sensitive to changes in weight loss, rate of weight regain and discounting rate. Although the non-pharmacological weight management programme in the comparator arm yielded higher weight losses than generally observed in clinical practice, these results demonstrate that additional sibutramine treatment is a cost effective therapy for an obese population without comorbidities in Germany. The CUA results are within the range generally accepted as cost effective and should be viewed as conservative when generalizing to settings offering standard non-pharmacological treatment.     

Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women

BACKGROUND: Dietary fat has been reported to influence insulin sensitivity. OBJECTIVE: The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity. DESIGN: Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss. RESULTS: The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) and similarly after weight loss in the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(-1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(-1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of the 2 decreased significantly only in the orlistat group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group. CONCLUSIONS: Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.     

Six-month treatment of obesity with sibutramine 15 mg; a double-blind, placebo-controlled monocenter clinical trial in a Hispanic population

OBJECTIVE: To evaluate the safety and efficacy of sibutramine 15 mg by mouth once per day in obese patients over a period of 6 months. RESEARCH METHODS AND PROCEDURES: A monocenter, double-blind, placebo controlled, parallel, prospective clinical trial was carried out. Sixty-nine male and female obese patients (body mass index [BMI] > 30 kg/m2) aged 16 to 65 years entered the trial. RESULTS: 22 of 35 patients in the sibutramine group and 9 of 34 patients in the placebo group completed the trial. The high dropout rate in the sibutramine group was due to adverse events in 3 cases, lack of efficacy (as judged by patients) in 7, loss to follow-up in 2, and an orthopedic device being worn in 1; in the placebo group the dropouts were ascribed to lack of efficacy (as judged by patients) in 17 cases and to loss to follow-up in 8 cases. Using the method of last observation carried forward, the weight loss in the sibutramine group was 10.27 kg (95% confidence intervals [95% CI] 7.66; 13.07) and 1.26 kg (95% CI 0.3; 2.23) in the placebo group. The BMI loss was 4.17 kg/m2 (95% CI 3.11; 5.22) in the sibutramine group and 0.53 kg/m2 (95% CI 0.13; 0.92) in the placebo group. The waist circumference reduction was 12.51 cm (95% CI 9.25; 15.77) in the sibutramine group and 3.26 cm (95% CI 1.38; 5.14) in the control group (p<0.05 by paired Student's t test for all the intragroup comparisons). Twenty-three sibutramine patients had 34 adverse events, the most frequent adverse events in the sibutramine group were upper respiratory tract infections (n = 6) and constipation (n = 6); 16 placebo patients had 21 adverse events. Three sibutramine patients withdrew their informed consent when they had adverse events. DISCUSSION: The results show that sibutramine induces significant loss of body weight and waist circumference. Cardiovascular function was not significantly affected by sibutramine. Sibutramine was well tolerated by most of the patients.     

Promoting more modest weight losses: a pilot study

OBJECTIVE: This pilot study assessed the short- and long-term effects of a modified cognitive behavioral treatment designed to facilitate obese patients' acceptance of a 5% to 10% reduction in initial weight. RESEARCH METHODS AND PROCEDURES: Participants were 17 women with a mean age of 46.5 +/- 9.7 years and BMI of 34.7 +/- 2.9 kg/m2. They participated in a 40-week program that included four phases. The first discussed the benefits of modest weight losses and the potential adverse effects of unrealistic expectations. Phase II provided instruction in traditional cognitive behavioral methods of weight control Phase III focused on methods to improve body image and self-esteem. Phase IV addressed skills for weight maintenance. Changes in weight, self-esteem, body image, and quality of life were assessed at the end of treatment and 1 year later (week 92). RESULTS: At week 40, participants lost an average of 5.7 +/- 5.3% of initial weight, which was associated with significant improvements in body image, self-esteem, and quality of life. Improvements in psychosocial status were maintained at week 92, although mean weight loss at this time had declined to 2.9 +/- 5.6% of initial weight. Increased satisfaction with body weight at week 40 was associated with significantly better maintenance of weight loss at follow-up (r = -0.70; p = 0.02). DISCUSSION: Having participants seek only modest initial weight losses does not appear to facilitate weight maintenance. However, increasing patients' satisfaction with their body weight at the end of treatment may help improve weight maintenance. More research is needed on the relation between satisfaction with initial weight loss and long-term success.     

Regulation of body weight and carcass composition by sibutramine in rats

OBJECTIVE: We examined the effectiveness of sibutramine to modulate food intake and body composition in rats with two levels of adiposity imposed by the duration of their maintenance on a moderate-fat diet. RESEARCH METHODS AND PROCEDURES: Male Sprague--Dawley rats were fed a 32% fat diet from weaning until 2 or 4 months of age, at which point, body fat was either 15% or 25%, respectively, as measured by DXA. Sibutramine (0.6 or 2 mg/kg, orally) was then given daily for 2 weeks. RESULTS: Food intake and body weight decreased acutely in a dose-related manner in both groups with sibutramine treatment. In all rats, food intake suppression was attenuated after multiple days of sibutramine. Both 15%- and 25%-fat rats had a persistent decrease in weight gain over the 2-week period in response to sibutramine. The older, 25%-fat rats were more sensitive to sibutramine than the younger, 15%-fat rats with regard to the magnitude of overall food intake inhibition, decrease in body weight gain, and caloric efficiency. Despite these differences, sibutramine produced the same relative reductions in fat mass and had no effect on lean mass in the two groups. DISCUSSION: Thus, sibutramine produced equivalent efficacy on carcass fat loss in both groups, despite less inhibition of feeding and body weight gain in leaner rats. Whether these changes are a result of the leaner rats being younger and on a steeper growth curve compared with older, fatter rats or whether this is a direct function of their level of adiposity remains to be determined.     

Management of obesity as a chronic disease: nonpharmacologic,pharmacologic, and surgical options

The successful management of obesity requires a long-term approach that is tailored to an individual's lifestyle and needs. Initial treatment should focus on lifestyle modifications-dietary interventions and increased physical activity-with behavioral modification strategies used adjunctively. Several antiobesity drugs are approved by the Food and Drug Administration for use in obese patients, as well as in overweight individuals with at least one obesity-related comorbidity. Most are approved only for short-term weight loss, but sibutramine and orlistat are approved for long-term weight loss and maintenance. In addition to weight reduction, in clinical trials these drugs provided beneficial actions on several cardiovascular risk factors. Several other drugs currently approved for other uses show promise in their ability to cause weight loss. Surgical options should be reserved for severely obese patients with significant medical comorbidities or physical conditions.     

A low-fat intake and greater activity level are associated with lower weight regain 3 years after completing a very-low-calorie diet

OBJECTIVE: To examine the roles of diet, exercise, and lifestyle factors in determining long-term weight regain after weight loss with a very-low-calorie diet (VLCD). SUBJECTS: Twenty-seven of 38 women who lost weight with a VLCD. DESIGN: Graduates of a weight loss intervention study returned for follow-up 3 years after program completion. Percentage of initial weight loss that was regained was correlated with subjects' fat intake (assessed via 7-day food records and a Diet Habit Survey), energy intake (assessed via 7-day food records), activity level and lifestyle factors (assessed via questionnaires) that are supportive of weight loss maintenance. STATISTICAL ANALYSES PERFORMED: Regression analysis was used to assess the relationship of weight regain with fat intake, activity level, and energy intake. Contingency table analysis was used to assess the association between weight regain and lifestyle factors. RESULTS: Subjects followed experienced a -20.7kg+/-9.2kg (-19.2%+/-7%) (mean+/-standard deviation) weight change during the original VLCD program and a 13.9kg+/-11.3kg (76.6%+/-52.1%) weight change 3 years post-VLCD. Fat intake, assessed by a 7-day food diary, was positively correlated with weight regain at 3 years (r=0.66, P=.0004). Less weight regain was also seen with a lower percent fat intake as reflected by a higher Diet Habit Survey score (r=-0.55, P=.004). Women with the lowest tertile of reported fat intake (<25% of energy) from the Diet Habit Survey regained the least amount of weight (P=.05). Activity level was negatively correlated with weight regain (r=-0.53, P=.005). After correction for multiple comparisons, there was no association between total energy intake and weight regain. Lifestyle factors were also not associated with weight regain.Applications/conclusions: Identifying strategies to maintain weight loss is crucial because of the negative health effects and increasing prevalence of obesity. For women who have lost weight on a VLCD, limiting dietary fat intake and maintaining physical activity are both important factors for the prevention of weight regain. To promote better weight loss outcomes, registered dietitians should help clients who have lost weight limit their fat intake to less than 30% of energy and encourage high activity levels.     

Impact of weight loss and regain on quality of life: mirror image or differential effect?

OBJECTIVE: To compare the impact of weight regain and weight loss on health-related quality of life. RESEARCH METHODS AND PROCEDURES: Subjects were 122 (106 women, 16 men) overweight and obese participants in a weight reduction program (phentermine-fenfluramine and dietary counseling) who had initially lost at least 5% of their total body weight and then regained at least 5% of their weight during the follow-up period. Follow-up periods ranged from 10 to 41 months (mean, 28 months). Participants completed the Impact of Weight on Quality of Life-Lite, an obesity-specific health-related quality of life (HRQOL) measure, at 3-month intervals. RESULTS: Mean BMI at baseline was 40.9 +/- 6.6 kg/m(2) (range, 29.2 to 63.7 kg/m(2)). Average weight loss from entry was 18.8 +/- 6.7% (range, 6.0% to 43.7%), and average regain was 10.1 +/-4.4% of baseline weight (range, 5.0% to 30.6%). The effects of weight regain on HRQOL mirrored the effects of weight loss-rates of HRQOL change were similar in magnitude but different in direction for comparable weight loss and regain. Those with more severe initial impairments in HRQOL experienced greater improvements in HRQOL during weight loss as well as greater deterioration during weight regain than those with less severe impairments. DISCUSSION: Weight loss and regain produced mirror image changes in HRQOL. The initial severity of HRQOL impairment had a greater impact on the magnitude of HRQOL change than the direction of weight change. Findings underscore the importance of maintaining weight loss for the purposes of retaining obesity-specific HRQOL benefits.