Anti-obesity Treatment Research Articles

Synthesis and Biological Evaluation of Novel Bouchardatine Derivatives as Potential Adipogenesis/Lipogenesis Inhibitors for Antiobesity Treatment.

Our recent study has shown that the natural product bouchardatine (1) can reduce the triglyceride (TG) content in 3T3-L1 adipocytes (EC50 ≈ 25 μM). Here, we synthesized two series of compounds by introducing amine side chains at the 5 or 8 position of 1 and evaluated the lipid-lowering activity of derivatives. It was found that some of the compounds had significant lipid-lowering effects, and the most active compound 3d showed better activity (EC50 = 0.017 μM) than 2 (EC50 = 0.086 μM), a compound reported by us. Further, the mechanism studies revealed that 3d blocked TG accumulation via activation of the LKB1-AMPK signaling pathway, efficiently down-regulating the expression of key regulators of adipogenesis/lipogenesis. Cell uptake assay and confocal imaging of 3d in cells indicated that compound 3d had favorable cell permeability. Our results suggest that 3d may be a promising agent for the treatment of obesity and related metabolic disorders.

New insights on the role of the endocannabinoid system in the regulation of energy balance.

Within the past 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, as it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories. An overactive endocannabinoid cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders. However, because of the psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as antiobesity treatment were removed from the European market in late 2008. Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders. These aspects will be especially highlighted in this review.

PP07.2 – 2774: Five-year follow-up of Fenfluramine as add-on treatment in Dravet syndrome

Objective Further evaluation of efficacy of fenfluramine in Dravet syndrome. Methods Dravet syndrome remains, notwithstanding the introduction of newer anti-epileptic drugs, a therapy resistant epilepsy syndrome. Fenfluramine is an amphetamine-like drug used in the past as part of anti-obesity treatment. Because of possible cardiac side effects (valve thickening, pulmonary hypertension), it has been withdrawn from the market in the US and Europe. In Belgium, it was allowed to study its potential anti-convulsive effect and possible side effects in a small group of well-defined patients with Dravet syndrome. Results Twelve patients, seven girls and five boys, with a genetically proven (11/12) diagnosis of Dravet syndrome received add-on therapy with fenfluramine. The retrospective data were published in 2012 (Ceulemans et al, Epilepsia 2012). We present here the results of 5 years (10 patients) and 4 years (2 patients) prospective follow-up. Overall, looking at the prospective period only, 50% (29/58) of the patient-years were seizure free years, and in 21% (12/58) were only rare seizures ( Conclusion These five-year prospective follow-up data confirms the promising results of fenfluramine as add on in Dravet syndrome. Patients were seizure free or only had rare seizures for at least one year in 71%. Valve thickening never seems a progressive problem and is never clinically significant.

Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration.

Obesity is a frequent metabolic disorder but an effective therapy is still scarce. Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity but are ineffective after peripheral application. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF-2 receptor. Peripheral administration of myristoylated and palmitoylated PrRP analogs to fasted mice induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight and improved metabolic parameters, and attenuated lipogenesis in mice with diet-induced obesity. Our data suggest that the lipidization of PrRP enhances stability and mediates its effect in central nervous system. Strong anorexigenic and body-weight-reducing effects make lipidized PrRP an attractive candidate for anti-obesity treatment.

Liraglutide and obesity: a review of the data so far.

The prevalence of obesity worldwide has nearly doubled since 1980 with current estimates of 2.1 billion in 2013. Overweight and obesity lead to numerous adverse conditions including type 2 diabetes, cardiovascular disease, stroke, and certain cancers. The worldwide spread of obesity and associated comorbidities not only threatens quality of life but also presents a significant economic burden. While bariatric surgery has proven to be a viable treatment option for the morbidly obese, there is clearly a need for less invasive alternatives. Recent research has suggested that long-acting analogs of the gut hormone, glucagon-like peptide 1 (GLP-1), may have potential as an antiobesity treatment. The GLP-1 receptor agonist, liraglutide (trade name Saxenda), was recently approved by the US Food and Drug Administration as an obesity treatment option and shown in clinical trials to be effective in reducing and sustaining body weight loss. This review presents the basis for GLP-1-based therapies with a specific focus on animal and human studies examining liraglutide’s effects on food intake and body weight.

2,4,6-Trihydroxybenzaldehyde, a potential anti-obesity treatment, suppressed adipocyte differentiation in 3T3-L1 cells and fat accumulation induced by high-fat diet in C57BL/6 mice

In the present study, 2,4,6-trihydroxybenzaldehyde (THB) was evaluated for inhibitory effects on adipocyte differentiation in 3T3-L1 cells and anti-obesity effects in mice with high-fat diet (HFD)-induced obesity. Lipid accumulation measurement indicated that THB markedly inhibited adipogenesis, and this involved down-regulation of the expression of the adipogenesis-related proteins, CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c), in 3T3-L1 pre-adipocyte cells. In a mouse model of HFD-induced obesity, oral administration of THB (5 and 25mg/kg for 13 weeks) reduced the HFD-induced increase in weight gain. THB administration also reduced serum levels of glucose, triglycerides, and total cholesterol. A reduction in the hypertrophy of white adipose tissue was also observed. Furthermore, THB administration inhibited HFD-induced hepatic steatosis. These results provided evidence that administration of THB alleviated HFD-induced obesity in C57BL/6 mice and revealed the potential of THB as a nutraceutical to help prevent or treat obesity and the associated metabolic disorders.

Weight Loss Pharmacotherapy of Obese Non-Diabetic and Type 2 Diabetic Patients

The first line in the treatment of obesity is a combination of a low calorie diet, increased physical activity and behavioural therapy. Unless these options fail, should be considered an effective and safe pharmacotherapy. The market situation in anti-obesity treatment will change in a relatively short time; the combination anti-obesity therapy is entering into clinical practice. Currently in Europe we have three drugs approved for long-term chronic treatment of obesity. In addition to the orlistat EMA approved a combination of naltrexon SR/bupropion SR and liraglutide 3.0 mg. A specific feature management of obese diabetic patients is the selection of weight neutral or weight-reducing anti-diabetic treatment (oral anti-diabetics, insulin), but also weight neutral treatment associated with co-morbidities.

New pharmacological perspectives for the leptin receptor in the treatment of obesity.

After its discovery in 1994, leptin became the great hope as an anti-obesity treatment based on its ability to reduce food intake and increase energy expenditure. However, treating obese people with exogenous leptin was unsuccessful in most cases since most of them present already high circulating leptin levels to which they do not respond anymore defining the so-called state of “leptin resistance.” Indeed, leptin therapy is unsuccessful to lower body weight in commonly obese people but effective in people with rare single gene mutations of the leptin gene. Consequently, treatment of obese people with leptin was given less attention and the focus of obesity research shifted toward the prevention and reversal of the state of leptin resistance. Many of these new promising approaches aim to restore or sensitize the impaired function of the leptin receptor by pharmacological means. The current review will focus on the different emerging therapeutic strategies in obesity research that are related to leptin and its receptor.

Off-label antiobesity treatment in patients without diabetes with GLP-1 agonists in clinical practice.

The aim of the work was to investigate whether continuation of treatment, side effects, and effect on weight loss of GLP-1 agonists in obese patients without diabetes are equally promising in daily clinical-practice-settings compared to controlled clinical trials. Obese patients without diabetes of our interdisciplinary obesity centre were treated off-label with GLP-1-agonists for different time periods. Application was started with low-dose and increased if side effects were tolerable. Monthly costs were € 125 for daily applications of 1.2 mg liraglutide or 10 μg exenatide twice daily. Data were obtained by telephone interviews about baseline characteristics, weight loss, sensation of satiation, duration of therapy, side effects, and reasons for discontinuation. Of 43 included cases (5 males, mean age 43±11 years, mean weight 107±24 kg, mean excess weight 35±21 kg) 7 were treated with exenatide and 36 with liraglutide. Excess weight loss in linear regression models was 6.7% per month (p <0.05) under control of age, sex, initial weight, and type of GLP-1 analogue treatment and did not significantly differ between liraglutide and exenatide. Overall, 58% of patients reported side effects mostly concerning the gastrointestinal tract. Surprisingly no patient reported vomiting. One patient developed a severe pancreatitis. At time of telephone interview only 30.2% were continuing treatment. Mean treatment duration was 2.98±2.71 months. Common reasons for discontinuation of treatment were no/little effect on weight loss (27.9%), intolerable side effects (20.9%), or financial reasons (14%). GLP-1 agonist treatment in obese patients without diabetes also correlates with significant weight loss in clinical practice. However, side effects and discontinuation of treatment are common. Therefore, long-term effect on weight loss might not be as promising as suggested by data from clinical trials.

Ginseng and obesity: Observations from assorted perspectives

Ginseng is a well known herb used for various purposes that possesses many beneficial effects for the human body and aids in recovery or cure for several diseases. There has been much research and many clinical trials designed to ascertain what these beneficial effects are. Studies have investigated ginseng effects on diabetes, osteoporosis, the immune system, and many other diseases. Research has also shown ginseng to be effective as an antiobesity treatment. Ginsenoside components inhibit differentiation inducers in adipocyte tissues. This review summarizes the in vivo and in vitro effects of various ginseng crude extracts/ginsenosides on obesity via activation of AMPK- and/or cAMP-dependent pathways, which are networks of transcription factors through which PPARγ and cofactors operate. Additional proteins, markers, and pathways are suggested for which the effects of ginseng saponins may be promising.

Potential pancreatic lipase inhibitory activity of an endophytic Penicillium species

Pancreatic lipase (PL) is considered as one of the safest target for diet-induced anti-obesity drug development. Orlistat is the only PL inhibitor approved for anti-obesity treatment till date. In the process of exploration of new PL inhibitors, we have screened culture filtrates of 70 endophytic fungi of medicinal plants using qualitative as well as quantitative in-vitro PL assays. The qualitative assays indicated potential PL inhibition in only three isolates, namely #57 TBBALM, #33 TBBALM and #1 CSSTOT. Only ethyl acetate extracts of the culture filtrates of these isolates exhibited the PL inhibition. #57 TBBLAM ethyl acetate extract of culture filtrate exhibited potential PL inhibition with an IC50 of 3.69 µg/ml which was comparable to the positive control, i.e. Orlistat exhibiting IC50 value of 2.73 µg/ml. Further molecular phylogenetic tools and morphological studies were used to identify the isolate #57 TBBALM as Penicillium species.

Nesfatin Role as Possible New Anti Obesity Treatment

In this article, we review on the current concepts about Nesfatin-1 as a new anti-obesity treatment and evaluate the existing issues in the context of this knowledge and the available literature. The intent is to enable clinicians to know Nesfatin-1 as a new anti-obesity treatment and make rational decisions based on this perspective as possible clinical application. Future research should seek to clarify whether Nesfatin-1 would be beneficial in the management of obesity.

Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor

BackgroundThere is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model.MethodsWe determined the inhibitory action of Anti-lipase IgY on lipase activity in vitro. We also focused our evaluation on the anti-obesity properties of Anti-lipase IgY in a murine high fat diet-induced obesity model.ResultsAnti-lipase IgY blocked porcine lipase activity with an IC50 of 0.49 μM. Supplementing the high fat diet with only 0.2% (w/w) of Anti-lipase IgY for 35 days significantly decreased the weights of intraperitoneal adipose tissues, epididymal, mesenteric, retroperitoneal and perirenal adipose tissues, and the amounts of hepatic total lipid, triglyceride, and cholesterol. This was accompanied by a significant increase in the fecal excretion of triglyceride in the absence of diarrhea. Furthermore, Anti-lipase IgY treatment restored body weight gain to levels similar to mice fed with Control IgY.ConclusionsThis study provides the first report of the development of anti-lipase IgY and the direct evidence that inhibition of pancreatic lipase using Anti-lipase IgY is an effective anti-obesity treatment due to the associated increase in fecal excretion of triglyceride.

Bofu-Tsu-Shosan, an Oriental Herbal Medicine, Exerts a Combinatorial Favorable Metabolic Modulation Including Antihypertensive Effect on a Mouse Model of Human Metabolic Disorders with Visceral Obesity

Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM) and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF) is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT) were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system.

Phentermine and Topiramate Extended-Release for the Obesity: New Kids on the Block

Obesity is a major public health concern associated with increased morbidity and mortality. Its prevalence is rising worldwide mainly due to modern lifestyle habits. Several mechanisms like inflammation, endothelial dysfunction, increased sympathetic tone, high leptin and insulin concentrations as well as enhanced thrombogenesis are implicated to the emergence and progress of cardiovascular disease. Although, changes in the lifestyle remain the cornerstone of antiobesity treatment, alone do not always provide the desired weight loss. Often, the addition of pharmacotherapy or bariatric surgery is considered the treating option for patients meeting eligibility criteria. Although, bariatric surgery is limited to patients with a high body mass index due to the risks of the procedures, the effects of anti-obesity medication on cardiovascular outcome are still unclear. Several anti-obesity drugs have been abandoned because of serious adverse events. Qsymia is a combination of phentermine and topiramate used for obesity treatment. Administration of this drug reduces body weight and has favorable effects in various metabolic and anthropometric parameters. However, there are concerns regarding cardiovascular safety of this drug. In this review, we are going to present the history of current antiobesity medication focusing on the combination of phentermine and topiramate and recent patents.

Treating the obese diabetic

Type 2 diabetes and obesity are intimately linked; reduction of bodyweight improves glycemic control, mortality and morbidity. Treating obesity in the diabetic is hampered as some diabetic treatments lead to weight gain. Bariatric surgery is currently the most effective antiobesity treatment and causes long-term remission of diabetes in many patients. However, surgery has a high cost and is associated with a significant risk of complications, and in practical terms only limited numbers can undergo this therapy. The choice of pharmacological agents suitable for treatment of diabetes and obesity is currently limited. The glucagon-like peptide-1 receptor agonists improve glycemia and induce a modest weight loss, but there are doubts over their long-term safety. New drugs such as lorcaserin and phentermine/topiramate are being approved for obesity and have modest, salutary effects on glycemia, but again long-term safety is unclear. This article will also examine some future avenues for development, including gut hormone analogues that promise to combine powerful weight reduction with beneficial effects on glucose metabolism.

Standardized Ethanol Extract of Curcuma longa L. Fermented by Aspergillus oryzae Promotes Lipolysis via Activation of cAMP-Dependent PKA in 3T3-L1 Adipocytes

We investigated the effect of standardized ethanol extract from Curcuma longa L. fermented by Aspergillus oryzae (FTE) on lipid accumulation and lipolysis using 3T3-L1 adipocytes. Treatment with FTE at 100 μg/mL significantly reduced lipid accumulation by 43% as quantified by Oil Red O dye and microscopic observation. Intracellular triglyceride content was also lowered by 60%. To determine the effects of FTE on lipolysis, levels of glycerol release and mRNA expression of lipases were measured. Incubation of 3T3-L1 adipocytes with 60 and 100 μg/mL FTE dramatically elevated levels of free glycerol released into the medium by 58 and 77%, respectively. Likewise, treatment of mature adipocytes with FTE significantly increased cAMP level by reduction of phosphodiestersae-3B. Subsequently, FTE clearly increased hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA levels and decreased perilipin mRNA level via cAMP-dependent protein kinase A (PKA), resulting in lipolysis. Practical Applications Turmeric (the common name for Curcuma longa L.) is an Indian spice derived from rhizomes of the plant Curcuma longa, a perennial member of the Zingiberaceae family cultivated in India and other parts of Southeast Asia. Turmeric has traditionally been used for the treatment of inflammation, menstrual disorders, dyspepsia, vomiting and cancer. In this study, FTE suppressed 3T3-L1 preadipocyte differentiation and promoted lipolysis via upregulation of mRNA levels of HSL and ATGL by PKA phosphorylation. Our results suggested that FTE could be a candidate for antiobesity treatment through reduction of lipid accumulation and stimulation of lipolysis.

Recent advancements in drug treatment of obesity

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

Irisin, a Novel Myokine Responsible for Exercise Induced Browning of White Adipose Tissue

Dear Sir, Exercise is known to induce weight loss which is more than expected due to energy expenditure during exercise. Till now the molecular mechanism of this disproportionate loss in weight was not known. A novel myokine, Irisin named after Greek goddess iris, discovered by Bruce M. Spiegelman et al. in 2012 [1] has been found to be the hormone responsible for exercise induced improvement in glucose homeostasis. It is a 112 AA polypeptide secreted from muscle into the bloodstream in response to exercise. There is 100 % homology in structure of Irisin between human and mice suggesting it to be a highly conserved hormone during evolution. It is found to be responsible for browning of subcutaneous adipose tissue and thus it is responsible for antiobesity and antidiabetic effect [1]. Regarding the biochemical nature, Irisin is a cleaved and secreted fragment of FNDC5 (FRCP2 and PeP). FNDC5 is synthesised as a type I membrane protein which undergoes proteolytic cleavage and this results in release of N terminal part of protein into extracellular space. FNDC5 consists of three parts, a signal peptide, two fibronectin domains, hydrophobic domain and a C-terminal peptide. FNDC 5 is a glycoprotein. It is released from muscle in response to exercise [2, 3]. As per the molecular mechanism, exercise is the stimulus for release of PGC1α (PPAR-co-activator-1α) which is a coactivator of PPAR γ (involved in energy metabolism). This in turn stimulates expression of FNDC5 which in turn is proteolytically cleaved to release the active hormone, irisin. Irisin has cell surface receptors. It increases the expression of UCP1 and Cidea mRNA, which causes browning of primarily subcutaneous and also of visceral adipose tissue and thereby inducing thermogenesis [4]. White adipose tissue, which is a storehouse of energy, is converted to brown adipose tissue which dissipates energy as heat. This in turn causes increase in total body energy expenditure. As far as the potential biochemical implication is concerned, Irisin causes browning of adipose tissue and thereby inducing thermogenesis, white adipose tissue is primarily composed of triglycerides and fatty acids (mainly responsible for insulin resistance). Irisin causes white adipose tissue to get converted to brown adipose tissue and thereby reduction of insulin resistance and improvement of glucose homeostasis. It may be useful as anti obesity treatment by weight loss and antidiabetic treatment by virtue of improved glucose homeostasis. To conclude, it may be useful in treatment of obesity, diabetes, and metabolic syndrome. It will be specially useful to people who cannot exercise because of physical limitations. However, it can not act as a substitute for exercise. All its effects are presently seen in mice, because of its 100 % sequence homology, it is being assumed to have same effect in humans for which clinical trials are being conducted (Fig. 1). Fig. 1 Mechanism of exercise induced weight loss by Irisin

500 Intragastric Balloons: What Happens 5 Years Thereafter?

The BioEnterics Intragastric Balloon (BIB) has been considered an effective, less invasive method for weight loss, as it provides a permanent sensation of satiety. However, various non-randomized studies suggest BIB is a temporary anti-obesity treatment, which induces only a short-term weight loss. The purpose of this study was to present data of 500 obese who, after BIB-induced weight reduction, were followed up for up to 5 years. The BioEnterics BIB was used, and remained for 6 months. At 6, 12, and 24 months post-removal (and yearly thereafter), all subjects were contacted for follow-up. From 500 patients enrolled, 26 were excluded (treatment protocol interruption); 474 thus remained, having initial body weight of 126.16 ± 28.32 kg, BMI of 43.73 ± 8.39 kg/m2, and excess weight (EW) of 61.35 ± 25.41. At time of removal, 79 (17%) were excluded as having percent excessive weight loss (EWL) of <20%; the remaining 395 had weight loss of 23.91 ± 9.08 kg (18.73%), BMI reduction of 8.34 ± 3.14 kg/m2 (18.82%), and percent EWL of 42.34 ± 19.07. At 6 and 12 months, 387 (98%) and 352 (89%) presented with weight loss of 24.14 ± 8.93 and 16.31 ± 7.41 kg, BMI reduction of 8.41 ± 3.10 and 5.67 ± 2.55 kg/m2, and percent EWL of 42.73 ± 18.87 and 27.71 ± 13.40, respectively. At 12 and 24 months, 187 (53%) and 96 (27%) of 352 continued to have percent EWL of >20. Finally, 195 of 474 who completed the 60-month follow-up presented weight loss of 7.26 ± 5.41 kg, BMI reduction of 2.53 ± 1.85 kg/m2, and percent EWL of 12.97 ± 8.54. At this time, 46 (23%) retained the percent EWL at >20. In general, those who lost 80% of the total weight lost during the first 3 months of treatment succeeded in maintaining a percent EWL of >20 long term after BIB removal: more precisely, this cutoff point was achieved in 83% at the time of removal and in 53%, 27%, and 23% at 12-, 24-, and 60-month follow-up. BIB seems to be effective for significant weight loss and maintenance for a long period thereafter, under the absolute prerequisite of patient compliance and behavior change from the very early stages of treatment.