Efficacy of High-dose Liraglutide 3.0 mg in Patients with Poor Response to Bariatric Surgery: Real-world Experience and Updated Meta-analysis.

PURPOSE: Poor response to bariatric surgery, characterized by insufficient weight loss (IWL) or weight regain (WR), poses a significant challenge in obesity treatment. This study aims to assess the effectiveness of liraglutide in addressing this issue. MATERIALS AND METHODS: A retrospective, multicenter cohort study investigated the impact of liraglutide 3 mg on weight loss in adults with suboptimal responses or weight regain after bariatric surgery (BS). Additionally, a systematic review and meta-analysis were conducted for a comprehensive evaluation. RESULTS: A total of 119 patients (mean age 41.03 ± 11.2 years, 71.4% female) who experienced IWL or WR after BS received pharmacologic therapy with liraglutide 3 mg. Mean percent weight loss in the entire cohort was 5.6 ± 2.6% at 12 weeks and 9.3 ± 3.6% at 24 weeks with a significant reduction in waist circumference (p < 0.0001). No serious side effects were reported. A meta-analysis, utilizing the fixed effect model with the metafor package in R, included 6 and 5 papers for the change in body weight and BMI after liraglutide treatment, respectively. The analysis demonstrated a considerable reduction in body weight (7.9; CI - 10.4; - 5.4, p < 0.0001) and BMI (3.09; CI 3.89; - 2.28, p < 0.0001). CONCLUSION: Liraglutide 3 mg emerges as a viable option for significant weight loss in patients experiencing IWL or WR after BS. Its inclusion in a multimodal, sequential obesity treatment approach proves promising.

Excessive generalized and visceral adiposity is associated with a higher prevalence of diabetic retinopathy in Caucasian patients with type 2 diabetes.

BACKGROUND AND AIMS: Type 2 Diabetes Mellitus (T2D) has heterogeneous clinical phenotypes related to different risk of developing diabetes complications. We investigated the correlation between generalized and abdominal adiposity and the prevalence of both micro- and macrovascular complications in Caucasian patients with T2D. METHODS AND RESULTS: We evaluated 769 individuals with T2D consecutively referred to our diabetes center. Body mass index (BMI), waist circumference (WC), waist to hip (W/H) ratio, glycated hemoglobin (HbA1c), systolic and diastolic blood pressure, lipid profile, smoking habit, diabetes therapy, and micro- and macrovascular complications were recorded. Patients were divided into three groups based on BMI and WC: non-obese with normal WC (nWC, n = 220), non-obese with excess of abdominal fat (AF, n = 260) and obese (Ob, n = 289). We found that nWC, compared with AF and Ob individuals, were predominantly males (p<0.01), had lower HbA1c (p<0.01), diastolic blood pressure (p<0.01), triglycerides (p<0.01), and showed a significantly lower prevalence of diabetic retinopathy (DR) (p = 0.01). The rate of proliferative DR was significantly higher in Ob (13.2 %) compared to the other groups (p = 0.03). Multivariate analyses showed a significantly decreased prevalence of DR in nWC compared to both AF (OR 0.58, 95 CI 0.34-0.96; p = 0.03) and Ob (OR 0.57, 95 CI 0.33-0.98; p = 0.04) individuals. Conversely, DR was associated, mainly in women, to higher WC and W/H ratio. The prevalence of the other diabetes-related complications was similar among the studied groups. CONCLUSIONS: In our population, nWC subjects showed a lower prevalence of DR. An increased generalized and abdominal adiposity was associated to a higher prevalence of DR, especially among females.

High-dose liraglutide improves metabolic syndrome in poor responders to bariatric surgery.

Background: Bariatric surgery (BS) represents the most effective therapy for obesity class III, or class II with at least one weight-related comorbidity. However, some patients have insufficient weight loss or clinically relevant weight regain after a successful primary procedure. This study aimed to assess the efficacy of liraglutide treatment on weight loss, body composition and improvement of metabolic syndrome (MS) in patients defined as poor responders after BS. Methods: The study involved 59 non-diabetic adults with obesity (M/F: 17/42, age: 38.6 ± 11.8 years, BMI 38.3 ± 5.5 kg/m2) who had been treated with BS and experienced a poor response, categorized as either IWL (insufficient weight loss) or WR (weight regain). All patients were prescribed pharmacological therapy with liraglutide and attended nutritional counseling. Anthropometric and clinical measurements, body composition and the presence of MS defined according to the ATP-III classification were evaluated before starting liraglutide and after 24 weeks of treatment. Results: After 24 weeks of treatment with liraglutide, the mean weight loss was 8.4% ± 3.6% with no difference between gender, bariatric procedure, or type of poor response (IWL or WR). A significant decrease in fat mass, free-fat mass and total body water was documented. After 24 weeks, patients presented significantly lowered fasting glucose, total cholesterol, triglycerides, AST and ALT. The prevalence of MS was reduced from 35% at baseline to 1.6% after 24 weeks. No patients discontinued the treatment during the study. Conclusion: In patients who experience poor response after BS, liraglutide is well tolerated and promotes significant weight loss, ameliorates cardiometabolic comorbidities, and reduces the prevalence of MS.

Effect of gluten-free diet on autoimmune thyroiditis progression in patients with no symptoms or histology of celiac disease: a meta-analysis.

Background: Hashimoto's thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other gluten-related conditions (GRC). In the last years, interest about gluten-free diet (GFD) has increased for its supposed extraintestinal anti-inflammatory effect; thus, many patients with HT initiate GFD on their own. Objectives: The aim of this meta-analysis is to examine all available data in literature about the effect of a GFD on TgAb, TPOAb, TSH, FT4, and FT3 levels in patients with HT and no symptoms or histology of CD. Methods: The study was conducted according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology). The search was performed on databases PubMed and Scopus. The last search was performed on 7 February 2023. Quality assessment was performed. Meta-analyses were performed using the random-effect model. Hedges' g was used to measure the effect size (ES). Statistical analyses were performed using StataSE 17. Results: The online search retrieved 409 articles, and 4 studies with a total of 87 patients were finally included for quantitative analysis. The risk of bias was generally low. The mean period of GFD was almost 6 months. The meta-analyses showed reduction in antibody levels with ES: -0.39 for TgAb (95% CI: -0.81 to +0.02; p = 0.06; I² = 46.98%) and -0.40 for TPOAb (95% CI: -0.82 to +0.03; p = 0.07; I² = 47.58%). TSH showed a reduction with ES: -0.35 (95% CI: -0.64 to -0.05; p = 0.02; I² = 0%) and FT4 showed an increase with ES: +0.35% (95% CI: 0.06 to 0.64; p = 0.02; I² = 0%). FT3 did not display variations (ES: 0.05; 95% CI: -0.38 to +0.48; p = 0.82; I² = 51%). The heterogeneity of TgAb, TPOAb, and FT3 data was solved performing sub-analyses between patients with or without GRC (TgAb p = 0.02; TPOAb p = 0.02; FT3 p = 0.04) and only for FT3, performing a sub-analysis between patients taking and not taking LT4 (p = 0.03). Conclusion: This is the first meta-analysis investigating the effect of GFD on HT. Our results seem to indicate a positive effect of the gluten deprivation on thyroid function and its inflammation, particularly in patients with HT and GRC. However, current lines of evidence are not yet sufficient to recommend this dietary approach to all patients with a diagnosis of HT.

Pharmacological treatment of nonresponders following bariatric surgery: a narrative review of the current evidence.

INTRODUCTION: Obesity is a complex chronic disease and requires a long-term multidisciplinary management. Even patients undergoing bariatric surgery, one the most effective treatments for obesity, can have insufficient weight loss (IWL) than expected (primary non responder) or weight regain (WR) after a successful primary procedure (secondary non responder). A poor response represents a challenge of bariatric surgery that can induce persistence or recurrence of obesity-related comorbidities, prejudicing benefits of surgery. Increasing evidence suggests that weight loss medications represent a useful strategy in obesity care also after bariatric surgery procedures. EVIDENCE ACQUISITION: This narrative review summarizes the evidence concerning anti-obesity therapy in the management of no-responders to primary bariatric surgery. Available data on liraglutide (one randomized double-blind placebo-controlled trial, three prospective and three retrospective studies), naltrexone/bupropion (three retrospective studies), orlistat (one case control prospective and one retrospective studies) and topiramate and phentermine (5 retrospective studies) have been considered. EVIDENCE SYNTHESIS: Available data suggest that weight loss medications could offer a significant adjunctive benefit to lifestyle and behavioral modifications in the life-long management of obesity. CONCLUSIONS: Newer treatment modalities including the use of anti-obesity drugs provide patients and healthcare providers with more options in the management of poor response after bariatric surgery.

Efficacy, renal safety and tolerability of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in elderly patients with type 2 diabetes: A real-world experience.

AIMS: To evaluate efficacy, renal safety and tolerability of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a cohort of patients with type 2 diabetes (T2DM) aged ≥65 years. METHODS: We retrospectively evaluated 364 elderly individuals with T2DM starting SGLT2i from June 2015 to June 2018. Patients were divided into 2 subgroups based on median age (70 years). Linear mixed effect models were used to estimate changes in glycated hemoglobin (HbA1c), body mass index (BMI), and glomerular filtration rate (eGFR). SGLT2i discontinuation rate and causes of treatment interruption were also recorded. RESULTS: A significantly higher percentage of patients achieved HbA1c <7.5% (46.7% vs. 31.6%, p < 0.01) and <8.0% (68.9% vs. 47.2%, p < 0.01) compared to baseline. Each year of therapy was associated with an average HbA1c decrease of 0.34% (p < 0.01) and BMI loss of 0.71 kg/m2 (p < 0.01), without significant interaction across age classes. In the younger group eGFR increased by 1.02 ml/min/year, while in the older group it declined by 0.42 ml/min/year (p = 0.08). Overall discontinuation rate during the follow-up period was similar across age groups (34.2% vs. 36.1%, long-rank p = 0.26). Genitourinary infections were the most frequent cause of treatment interruption (15.8% vs. 17.2%, p = 0.69) in both study groups, while persistent eGFR decline (4.4%) and orthostatic hypotension (1.7%) were only present in older age class. CONCLUSIONS: Efficacy, renal safety and tolerability of SGLT2i were similar in people >70 compared to 65-70 years of age, suggesting that a wider use should not be worried even in the elderly. However, some caution must be paid to the occurrence of persistent eGFR decline and orthostatic hypotension, especially in patients >70 years old.

Prevalence and Clinical Characteristics of Children and Adolescents with Metabolically Healthy Obesity: Role of Insulin Sensitivity.

Obesity represents a major risk factor for metabolic disorders, but some individuals, "metabolically healthy" (MHO), show less clinical evidence of these complications, in contrast to "metabolically unhealthy" (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment-insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.

The prevalence of chronic kidney disease and screening of renal function in type 2 diabetic patients in Finnish primary healthcare.

AIMS: To estimate the prevalence of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) in Finnish primary healthcare, and to evaluate the screening for CKD and the proportions of patients receiving antihyperglycemic and cardiovascular preventive medication. MATERIAL AND METHODS: T2D patients treated at the Rovaniemi Health Center, Finland during the years 2015-2019. Data included patient characteristics, blood pressure, HbA1c, lipid levels, kidney function and albuminuria, and medications prescribed. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.72 m2 and/or albuminuria. RESULTS: The study population comprised of 5112 T2D patients with a mean (SD) age of 66.7 (13.0) years. Of these, 60.2% were screened for CKD with both eGFR and albuminuria, and 30.1% of these patients had CKD. The prevalence of moderately increased and severely increased albuminuria was 19.6% and 3.2%, respectively. A total of 57.0% of the study population received angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). CONCLUSIONS: Screening for CKD with both recommended measures (eGFR and albuminuria) was insufficiently performed among this T2D population. Additionally, just over half of the study population had been prescribed ACE inhibitors or ARB. These results suggest an incongruity between the gold standard of diabetes care and real-world clinical practice.

Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review.

Alzheimer's disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders.

The novel loss of function Ile354Val mutation in PPARG causes familial partial lipodystrophy.

AIMS: Familial partial lipodystrophy (FPLD) is a rare autosomal dominant disorder, mostly due to mutations in lamin A (LMNA) or in peroxisome proliferator-activated receptor gamma (PPARG) genes. In the present study, we aimed to identify and functionally characterize the genetic defect underlying FPLD in an Italian family presenting with several affected individuals in three consecutive generations. METHODS: Mutational screening by direct Sanger sequencing has been carried out on both LMNA and PPARG genes. In silico analyses and functional in vitro studies on transfected cell lines have been also performed to evaluate the biological impact of the identified mutation. RESULTS: We identified a novel PPARG missense mutation (i.e., PPARγ2 Ile354Val) segregating with FPLD in the study family. In silico analyses and in vitro experiments showed that probably altering the PPARγ2 ligand binding domain conformation, the Ile354Val aminoacid change leads to a significant reduction (i.e., ~ 30-35%) of transcriptional activity in the mutant receptor, with no evidences of a dominant negative effect on the wild-type receptor. CONCLUSIONS: Our present data extend the spectrum of PPARG mutations responsible for FPLD3 and reinforce the notion that even loss of function mutations affecting transcriptional activity to an extent lower than that observed in the case of haploinsufficiency are able to cause a severe FPLD3 phenotype.

Impact of unhealthy childhood and unfavorable parents' characteristics on adiposity in schoolchildren.

BACKGROUND: Childhood obesity is encouraged by low physical activity (PA), time spent using screens (screen time, ST), and by sugar-sweetened beverage consumption (SSBc). It is also influenced by unfavorable parents' characteristics, such as a high body mass index (BMI) and low education level (EL). Our aim was to evaluate the overall and specific influence of these factors on childhood adiposity. MATERIAL AND METHODS: Anthropometric parameters including BMI z-score, waist circumference (WC), waist to height ratio (WtHR), and fat mass were measured in a cohort of 1702 schoolchildren (6.0-14.5 years, mean 10.7 ± 1.8) and questionnaires concerning children's PA, ST, and SSBc, and parent's BMI and EL were administered to parents. RESULTS: Overweight/obesity prevalence was higher (P < .0001) in males (57%) than in females (43%). Less physically active children (28.9%) had a higher prevalence of overweight/obesity and higher BMI z-score, WC, WtHR, and fat mass relative to more physically active children (P < .05). PA was negatively associated with the BMI z-score (r = 0.18, P < .0001) and fat mass percentage (r = 0.18, P < .0001). Children with more ST had higher WC and WtHR than non-ST viewers (P < .05) but not BMI. Moreover, SSBc did not influence the anthropometric parameters. At multivariate analysis, male gender, less PA, and parental risk factors (parent's overweight/obesity and low/medium EL) were independently associated with overweight and obesity among childhood with a progressively increasing odds ratio (1.65, 1.40, and 1.80, respectively). CONCLUSIONS: Male gender, behavioral risk factors (particularly low PA), and parent's characteristics are important correlates of obesity in children.

Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk.

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.

Type 2 Diabetes Mellitus and Alzheimer's Disease: Role of Insulin Signalling and Therapeutic Implications.

In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer's disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid ß accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment.

Strong evidence of sexual dimorphic effect of adiposity excess on insulin sensitivity.

AIMS: Our aims were to investigate in several large samples, with a wide range of adiposity, whether: (1) the effect of BMI on insulin sensitivity is different between sexes; (2) also waist circumference plays a sex-specific role on insulin sensitivity; and (3) serum adiponectin and resistin are mediators of such sex-dimorphic effect. METHODS: Samples used were: Gargano study 1 (GS1), GS2 and Catania study (CS) comprising 3274 individuals. Adiponectin and resistin were measured by ELISA. Associations between variables were tested by linear models. RESULTS: In all samples, relationship between BMI and HOMAIR was steeper in males than in females (BMI-by-sex interaction p = 0.04-0.0007). No interaction was observed on serum adiponectin and resistin (p = 0.40-059), which are therefore unlikely to mediate the sex-dimorphic effect of BMI on insulin resistance. Relationship between waist circumference and HOMAIR was similar between sexes in GS1 and GS2 but not in CS (waist-by-sex interaction p = 0.01), comprising much heavier individuals. This suggests that a sex-dimorphic effect of abdominal adiposity on insulin resistance is observable only in the context of high BMI. CONCLUSIONS: Our findings represent a proof of concept that BMI and insulin sensitivity are associated in a sex-specific manner. This may explain why females are protected from diabetes and cardiovascular disease, compared to males of similar BMI.

Very severely obese patients have a high prevalence of type 2 diabetes mellitus and cardiovascular disease.

The prevalence of very severe obesity has increased progressively and faster than other classes of obesity over the last years. It is unclear whether the prevalence of obesity-related complications and health risks increases progressively or reaches a plateau above a certain degree of obesity. The aim of our study was to investigate whether the severity of obesity was correlated with the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose, impaired glucose tolerance (IGT), metabolic syndrome (MS), and cardiovascular diseases (CVDs) in a large cohort of patients with different degrees of obesity. A cross-sectional study was conducted in 938 obese patients without a previous diagnosis of diabetes. Patients were assigned to different categories of obesity: mild-moderate obesity (BMI 30-39.9 kg/m(2)), morbid obesity (BMI 40-49.9 kg/m(2)), and super-obesity (SO, BMI ≥50 kg/m(2)). The prevalence of IGF, IGT, screen-detected T2DM, MS, and CVD was higher in SO patients than in the other groups. Interestingly, the association between SO and either MS or CVD was independent of glucose tolerance status, indicating that factors other than glucose metabolism also favor cardio-metabolic complications in obese patients. In patients without screen-detected T2DM (n = 807), insulin sensitivity and secretion OGTT-derived indexes indicated that SO patients had the worst glucose homeostasis relative to the other categories of obesity, which was indicated by the most reduced disposition index in these patients, a predictor of future T2DM. In conclusion, SO patients have an extremely high prevalence of glucose metabolism deterioration, and cardio-metabolic complications are more prevalent in these patients compared to less obese patients.

Intragastric balloon in association with lifestyle and/or pharmacotherapy in the long-term management of obesity.

BACKGROUND: Intragastric balloon (BioEnterics Intragastric Balloon, BIB®) or pharmacotherapy are possible options for the treatment of obese patients when traditional approaches have failed. The aim of our study was to compare in obese patients the effect on weight loss and metabolic changes of lifestyle modifications associated with either BIB or pharmacotherapy or the two treatments in sequence as a maintenance strategy for weight loss. METHODS: Fifty obese patients were recruited and randomly assigned to lifestyle modifications combined with either BIB for 6 months (n = 30) or sibutramine (pharmacotherapy group) for 1 year (n = 20). After BIB removal, patients were randomly assigned to either correct lifestyle (BIB/lifestyle) or lifestyle plus pharmacotherapy (BIB/pharmacotherapy). RESULTS: At 6 months, patients treated with BIB lost significantly (P < 0.05) more weight (percent of initial weight lost, %IWL = 14.5 ± 1.2; percent of excess BMI lost, %EBL = 37.7 ± 3.2) than patients who received pharmacological treatment (%IWL = 9.1 ± 1.5, %EBL = 25.3 ± 4.1). At 1 year, the weight lost was significantly (P < 0.05) greater in patients treated with either BIB/pharmacotherapy (%IWL = 15.8 ± 2.3%, %EBL = 41.3 ± 6.7%) or BIB/lifestyle (%IWL = 14.3 ± 2.7, %EBL = 34.9 ± 6.5%) in respect to pharmacotherapy group (%IWL = 8.0 ± 1.4%, %EBL = 22.1 ± 3.9%). Moreover, patients treated sequentially with BIB/lifestyle or BIB/pharmacotherapy showed a significant (P < 0.05) improvement in insulin sensitivity and triglycerides levels. CONCLUSIONS: BIB represents an efficacious long-term obesity treatment when supplemental strategies, as lifestyle modifications or pharmacotherapy, are established for weight maintenance after its removal.