Weight Regain Research Articles

Bariatric and endo-bariatric interventions for diabetes: What is the current evidence?

Bariatric interventions have shown the best therapeutic benefits in individuals with obesity. They can be classified into surgical procedures (bariatric/metabolic surgery) and endoscopic procedures. Common surgical procedures include sleeve gastrectomy, Roux-en-Y gastric bypass, bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing Surgery. Endoscopic procedures include intragastric balloons, transpyloric shuttle, endoscopic gastroplasties, aspiration therapy, duodenal mucosal resurfacing, duodeno-jejunal bypass liner, gastro-duodeno-jejunal bypass and incisionless magnetic anastomosis system among others. However, these procedures are limited by lack of wide availability, high costs, immediate and long-term complications and poor acceptability in some regions. Weight re-gain is a common concern and revisional metabolic surgery is often required. Appropriate pre-operative evaluation and correction of nutritional deficiencies post-surgery are very important. The most appropriate procedure for a person would depend on multiple factors like the intended magnitude of weight-loss, comorbidities and surgical fitness, as well as choice of the patient. Recently, glucagon-like insulinotropic peptide-1 receptor agonists (GLP) and the GLP-1/gastric inhibitory polypeptide co-agonist–Tirzepatide have shown remarkable weight loss potential, which is at par with bariatric interventions in some patients. How far these can help in avoiding invasive bariatric procedures in near future remains to be explored. An updated and comprehensive clinical review by He et al in the recent issue of World Journal of Diabetes address has addressed the avenues and challenges of currently available bariatric surgeries which will enable clinicians to make better decisions in their practice, including their applicability in special populations like the elderly and pediatric age groups, type 1 diabetes mellitus, and non-diabetics.

A02 - BS Ethnic and Social Deprivation Influence Weight Regain Following Roux En-Y Gastric Bypass

Abstract Background Weight regain is a prevalent issue following Roux-En-Y Gastric Bypass (RYGB) surgery for obesity. This study aims to assess the impact of ethnicity and social deprivation on the likelihood of weight regain post-RYGB. Method We analysed data from Luton & Dunstable Hospital. Key variables included patient demographics such as sex, age, ethnicity, social deprivation (Indices of Multiple Deprivation – IMD), American Society of Anesthesiologists (ASA) classification, and weight and Body Mass Index (BMI) at the time of surgery. Weight regain was defined as the regaining of more than 25% of the Total Body Weight Loss (TBWL) achieved after RYGB. Results Out of 1,346 patients who underwent RYGB, 80% were female. The median age was 48 years (IQR: 39-55), and the median BMI was 44.7 kg/m^2 (IQR: 40.6-50.1). At a median follow-up of 39 months, 20.7% experienced weight regain. Multivariable analysis showed that patients from Black (HR: 1.63, 95% CI: 1.33-1.81, p=0.009) and Asian (HR: 1.40, 95% CI: 1.23-1.71, p=0.011) ethnic groups, as well as those from more socially deprived backgrounds (HR: 2.39, 95% CI: 1.99 – 3.13, p<0.001), were more likely to experience weight regain compared to their White and more affluent counterparts. Conclusion Ethnicity and social deprivation significantly influence the likelihood of weight regain following RYGB. The factors contributing to these disparities are likely multifaceted, encompassing genetic, social, and educational elements. Early identification of patients at increased risk of weight regain and the provision of tailored resources can help mitigate this risk and enhance surgical outcomes.

Abstract 4123814: Long-term Incidence of Cardiovascular Events and Mortality in Patients with and without Weight Regain After Bariatric Surgery in the Swedish Obese Subjects Study

Background: Obesity shortens life expectancy, while bariatric surgery causes large weight loss and increases median life expectancy by approximately 3 years. However, weight regain after bariatric surgery is common, and its impact on health remains uncertain. In this study, we examined whether weight regain following bariatric surgery is associated with long-term cardiovascular outcomes and mortality. Methods: We analyzed patients undergoing bariatric surgery in the prospective Swedish Obese Subjects study, aged 37-60 with a BMI≥34 (men) or ≥38 (women), recruited 1987-2001. Patients who regained ≥20% of their 1-year weight loss after 4 years (regain group; n=715) were compared to those who regained less (maintenance group; n=631). Information on cardiovascular disease as well as overall and cardiovascular mortality was obtained from the Swedish Population and Address Register, the Swedish Cause of Death Register, and the Swedish National Patient Register. Median follow-up was 27 years. Results: Average weight change from year 1 to year 4 was +12.8 kg and -0.2 kg in the regain and maintenance groups, respectively. The incidence of major adverse cardiovascular events (myocardial infarction, stroke and heart failure) was similar between the groups, with 185 events in the regain group and 137 in the maintenance group. This corresponds to 11.6 events per 1000 person-years (95% CI: 10.1-13.5) for the regain group, and 10.0 events per 1000 person-years (95% CI: 8.3-12.4) for the maintenance group. The adjusted HR was 1.16 (95% CI: 0.92-1.46), p=0.213. During follow-up, there were 216 deaths in the regain group and 184 in the maintenance group, resulting in nearly identical overall mortality rates of 12.4 per 1000 person-years for both groups (95% CI for regain: 10.9-14.2, maintenance: 10.9-14.3). The number of deaths from cardiovascular disease was 77 in the regain group and 57 in the maintenance group, corresponding to similar incidence rates of 4.4 per 1000 person-years (95% CI: 3.5-5.5) and 3.8 per 1000 person-years (95% CI: 3.0-5.0), respectively (p=0.550). Conclusions: The incidence of major adverse cardiovascular events, as well as total and cardiovascular mortality, was similar between the weight regain and maintenance groups. This suggests that the beneficial association between bariatric surgery and reduced cardiovascular events persists despite weight regain.

A Very Low-Calorie Ketogenic Diet Approach for Post-Bariatric Weight Regain: A Pilot Study

Weight regain (WR) after bariatric surgery, particularly sleeve gastrectomy, is a significant challenge, often driven by a combination of metabolic, behavioral, and lifestyle factors. Non-surgical interventions to manage WR are critical, given the increased risks and reduced efficacy of revisional surgeries. In this context, very low-calorie ketogenic diets (VLCKDs) have gained attention for their potential to promote weight loss and improve body composition in individuals struggling with WR. This study assessed the safety and efficacy of a VLCKD in 11 patients who experienced WR following sleeve gastrectomy. Over an 8-week period, patients demonstrated a significant average weight loss of 6.3% (p = 0.005), along with improvements in body composition, including reductions in body fat percentage (p = 0.003) and waist circumference (p = 0.003). Metabolic markers, such as insulin resistance (HOMA-IR), also improved significantly (p = 0.041). Although a decrease in the glomerular filtration rate was observed (p = 0.007), this finding is unlikely to be clinically relevant over the short term. Importantly, no major adverse events were reported, with only mild constipation observed. These results suggest that VLCKDs may be a promising non-surgical approach for managing WR post-bariatric surgery, though further studies are needed to assess long-term effects, especially on renal function.

A Systematic Review Exploring Dietary Behaviors, Psychological Determinants and Lifestyle Factors Associated with Weight Regain After Bariatric Surgery

Background: Weight regains after bariatric surgery presents a significant challenge to long-term weight management and overall health outcomes. While clinical and surgical factors influencing bariatric outcomes have been extensively reviewed, there remains a notable gap in understanding how behavioral factors—specifically dietary habits, psychological influences, and lifestyle choices—impact long-term weight maintenance. This systematic review addresses this gap, highlighting the unique role of these behavioral factors in sustaining weight loss post-bariatric surgery. Aim: This systematic review aims to explore the behavioral factors—including dietary, psychological, and lifestyle influences—associated with weight regain after bariatric surgery. Methods: A comprehensive search was conducted across multiple databases, focusing on peer-reviewed articles published in English. We included observational studies exclusively focused on adults who experienced weight regain after bariatric surgery, with an emphasis on behavioral factors. Searches were conducted in MEDLINE via PubMed, Embase, Web of Science, Scopus, and Google Scholar, with the last search completed on 10 July 2024. Studies published within the past 10 years were considered. The Joanna Briggs Institute (JBI) critical appraisal tool for cross-sectional studies was used to assess the risk of bias. A total of 16 studies met the inclusion criteria: 12 cross-sectional studies, 3 cohort studies, and 1 in-depth interview study. Results: The review found inconsistencies in the definitions of weight regain across studies. Nonetheless, three primary behavioral factors were identified as potentially contributing to weight regain: dietary non-adherence and eating patterns, psychological determinants, and lifestyle behaviors. Dietary non-adherence included high-calorie food consumption, excessive intake of sweets, carbohydrates, and sweetened beverages, and low protein intake. Psychological factors such as depression, anxiety, emotional eating, and binge eating were prevalent among individuals experiencing weight regain. Lifestyle behaviors, including physical inactivity, smoking, and sedentary habits, also played significant roles. Conclusions: Post-bariatric weight management is multifaceted, necessitating a comprehensive approach that addresses dietary, psychological, and lifestyle factors. Most studies on behavioral factors linked to weight regain were cross-sectional with small sample sizes, limiting the ability to infer causality. Future research should include detailed information on dietary adherence, standardized tools to assess physical activity and sedentary behavior, and validated measures for psychological health. Tailored interventions and continuous support from healthcare professionals are essential for maximizing the effectiveness of bariatric surgery, promoting sustainable weight loss, and enhancing overall health outcomes.

S1515 The Role of Endoscopic Submucosal Dissection, Pursestring Suturing, and Anti-Obesity Medications in Enhancing Weight Loss After Transoral Outlet Reduction in Roux-en-Y Gastric Bypass Patients With Weight Regain

S1515 The Role of Endoscopic Submucosal Dissection, Pursestring Suturing, and Anti-Obesity Medications in Enhancing Weight Loss After Transoral Outlet Reduction in Roux-en-Y Gastric Bypass Patients With Weight Regain

Endoscopic argon plasma coagulation (APC) vs glucagon-like peptide-1 receptor agonists (ARGLP1) liraglutide and semaglutide for the treatment of weight regain (WR) after bariatric surgery (BS).

Endoscopic argon plasma coagulation (APC) vs glucagon-like peptide-1 receptor agonists (ARGLP1) liraglutide and semaglutide for the treatment of weight regain (WR) after bariatric surgery (BS).

S1519 Weight Regain After Endoscopic Sleeve Gastroplasty (ESG): Can Redo ESG (R-ESG) Help? What is the Role of Pharmacotherapy? Analysis of 80 Patients

S1519 Weight Regain After Endoscopic Sleeve Gastroplasty (ESG): Can Redo ESG (R-ESG) Help? What is the Role of Pharmacotherapy? Analysis of 80 Patients

S1513 Revisional Endoscopic Sleeve Gastroplasty/Endoscopic Sleeve-in-Sleeve Versus Surgical Re-Sleeve Gastrectomy in the Management of Weight Regain After Primary Sleeve Gastrectomy

S1513 Revisional Endoscopic Sleeve Gastroplasty/Endoscopic Sleeve-in-Sleeve Versus Surgical Re-Sleeve Gastrectomy in the Management of Weight Regain After Primary Sleeve Gastrectomy

S1598 Efficacy of Transoral Outlet Reduction for Weight Regain Following Roux-en Y Gastric Bypass: A Comparison of Pre and Post COVID-19 Pandemic

S1598 Efficacy of Transoral Outlet Reduction for Weight Regain Following Roux-en Y Gastric Bypass: A Comparison of Pre and Post COVID-19 Pandemic

Patient and healthcare practitioner evaluation of patient-reported outcomes in bariatric surgery - a modified Delphi study.

Patient-reported outcomes are an important emerging metric increasingly utilised in clinical, research and registry settings. These outcomes, while vital, are underutilised and require refinement for the specific patient population of those undergoing bariatric surgery. This study aimed to investigate and compare how pre-surgical patients, post-surgical patients, and healthcare practitioners evaluate patient-reported outcomes of bariatric surgery to identify outcomes that are considered most important. A modified Delphi survey was distributed to patients pre- and post-surgery, and to a variety of healthcare practitioners involved in bariatric care. Across two rounds, participants were asked to rate a variety of physical and psychosocial outcomes of bariatric surgery from 0 (Not Important) to 10 (Extremely Important). Outcomes rated 8-10 by at least 70% of participants were considered highly important (prioritised). The highest-rated outcomes were compared between the three groups as well as between medical and allied health practitioner subgroups. 20 pre-surgical patients, 95 post-surgical patients, and 28 healthcare practitioners completed both rounds of the questionnaire. There were 58 outcomes prioritised, with 21 outcomes (out of 90, 23.3%) prioritised by all three groups, 13 (14.4%) by two groups, and 24 (26.7%) prioritised by a single group or subgroup. Unanimously prioritised outcomes included 'Co-morbidities', 'General Physical Health', 'Overall Quality of Life' and 'Overall Mental Health'. Discordant outcomes included 'Fear of Weight Regain', 'Suicidal Thoughts', 'Addictive Behaviours', and 'Experience of Stigma or Discrimination'. While there was considerable agreement between stakeholder groups on many outcomes, there remain several outcomes with discordant importance valuations that must be considered. In particular, healthcare practitioners prioritised 20 outcomes that were not prioritised by patients, emphasising the range of priorities across stakeholder groups. Future work will consider these priorities to ensure resulting measures encompass all important outcomes and are beneficial and valid for end users.

Weight Regain Following Laparoscopic Sleeve Gastrectomy in Morbid Obesity

Weight Regain Following Laparoscopic Sleeve Gastrectomy in Morbid Obesity

Abstract P352: Transcriptomic Effects of Prolonged Diet-Induced Obesity in Subtypes of Agouti-Related Peptide Neurons of the Hypothalamic Arcuate Nucleus

Obesity is the greatest impediment to improving cardiovascular health. Despite many methods to lose weight, few people can keep it off in the long-term. The adaptation (suppression) of resting metabolic rate (RMR) appears to mediate weight re-gain after weight loss, yet the neurobiology that controls RMR remains unclear. Previously we published that the angiotensin II type 1 receptor (AT 1 R/ Agtr1a ) within Agouti-related peptide (AgRP/ Agrp ) neurons of the arcuate nucleus of the hypothalamus (ARC) is critical for integrative control of RMR. In the ARC, AT 1 R is only expressed by a subset of AgRP neurons (“Type 1”). In lean animals, AT 1 R inhibits this cell via a β-arrestin-1/Gαi-coupled cascade ("Type 1i”). Prolonged diet-induced obesity (DIO) causes RMR adaptation and is associated with a spontaneous G protein cascade switch by AT 1 R in the Type 1 neuron, in which AT 1 R activation begins stimulating the cell via the Gαq-coupled cascade (“Type 1s”). Our ongoing work aims to clarify the molecular mechanisms that govern AT 1 R coupling to Gαi versus Gαq within Type 1 AgRP neurons. First, using a dual-reporter mouse with tdTomato in AT 1 R-expressing cells plus green fluorescent protein in somatostatin (SST/ Sst )-expressing cells, we confirmed that SST expression is a selective marker of the Type 1 subtype of ARC AgRP neurons. Second, we reanalyzed our previously published single-nucleus RNA sequencing dataset describing the mouse ARC following prolonged DIO (PMC7347451) to explore the effects of DIO upon the transcriptomic profiles of AgRP neuron subtypes. Of 26 cell types initially identified, one cluster strongly expressed both Sst and Agrp (Cluster 5). Sub-clustering of Cluster 5 identified four cell types with strong Agrp expression (subclusters 0, 2, 5, and 6). Subcluster 6 may represent the Type 1i subtype due to high Sst expression, as well as enrichment for signatures of Gαi signaling events . Subcluster 6 also had very few DIO-induced differentially expressed genes (up=3, down=2). Interestingly, Subcluster 2 was comprised almost exclusively of nuclei from the DIO group (95%). Subcluster 2 was more closely related to Subcluster 6 than the other Agrp subclusters in the cluster phylogenetic tree, leading us to hypothesize that this cluster represents the DIO-induced Type 1s subtype. These data identify novel markers of AgRP neuron subtypes within the ARC, and a possible transcriptomic signature of subtype switching induced by prolonged DIO.

Pre-Surgery Cortisol Levels as Biomarker of Evolution after Bariatric Surgery: Weight Loss and Weight Regain.

Background: Bariatric surgery (BS) is effective for achieving significant weight loss. However, weight regain (WR) is an emerging problem. Objective: To assess the prognostic value of morning serum cortisol, a 1 mg dexamethasone suppression test (DST), 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) in a cohort of patients with severe obesity (pwSO) undergoing BS in terms of weight loss and WR. Methods: Patients scheduled for BS underwent the following procedures at baseline, 12 months and 24 months after BS: medical history, anthropometric data, blood analysis and cortisol tests. We evaluated total weight loss (TWL) ≥ 30% at 1 year and WR after 2 years as an increase of ≥10% of the maximum weight lost. Results: In total, 142 subjects were included; 101 (71.1%) were females and the mean age was 45.9 ± 9.2 years. Up to 76.8% of subjects achieved ≥30% TWL, without statistically significant differences in DST results or morning serum cortisol, UFC or LNSC levels. However, a higher pre-surgery morning serum cortisol level was a significant predictor of a WR ≥ 10% (cortisol 17.8 [IQR 13.1-18.5] vs. 12.0 [IQR 8.8-15.8] μg/dL; p < 0.01); OR of 1.216 (95% CI 1.069-1.384); AUC [0.761, CI: (0.616-0.906); p < 0.01]. A cut-off value of cortisol > 13.0 μg/dL was predictive of a WR ≥ 10% (sensitivity 0.71; specificity 0.63). Conclusions: No cortisol test was useful in predicting weight loss; however, the pre-surgery morning serum cortisol level was able to predict a WR ≥ 10% in a cohort of pwSO 2 years after BS. A cut-off value of cortisol > 13 μg/dL might be an easy tool to identify patients at higher risk of WR, enabling healthcare providers to implement tailored, long-term strategies to minimize this outcome.

Weight Regain following Bariatric Surgery and in vitro Fertilization Outcomes

Introduction: The aim of this study was to estimate the time to pregnancy and live birth and evaluate the effect of weight regain in women with a history of bariatric surgery (BS) who underwent in vitro fertilization (IVF) treatments. Methods: This is a retrospective cohort study. All patients with previous BS who underwent IVF treatment in a tertiary university-affiliated hospital between 2013 and 2022 were included. Time to pregnancy and live birth were compared between patients who regained less than or greater than three points of body mass index (BMI) from the nadir weight after BS. Kaplan-Meier curves and log-rank tests were used to compare groups. Results: A total of 78 patients were included in this study. The positive β-hCG, clinical pregnancy, and live birth rates following BS were 89.4%, 78.9%, and 50.8%, respectively. The median time from the beginning of IVF treatments to a positive β-hCG test was 2.97 months (95% CI: 1.04–4.89 months), to a clinical pregnancy was 7.1 months (95% CI: 3.56–10.91), and to a live birth was 20.2 months. Women who maintained their nadir BMI following BS had nearly twice the chance of achieving a clinical pregnancy (HR 1.967, 95% CI: 1.026–3.771, p = 0.042) and were approximately three times more likely to achieve a live birth (2.864, 95% CI: 1.196–6.859, p = 0.018) than those who regained at least three points of BMI. Conclusion: Weight regain after BS is associated with a lower rate of live births and prolonged time to achieve clinical pregnancy and live birth.

Reply to Pantelis, A.G. Comment on "Salazar et al. Weight Regain after Metabolic Surgery: Beyond the Surgical Failure. J. Clin. Med. 2024, 13, 1143".

We want to express our sincere gratitude for Dr. Pantelis' time and interest in reviewing our article and providing valuable feedback [...].

Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.

The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55years, with a mean body mass index (BMI) of 39.4kg/m2, and had BS surgery 5years prior. Over a mean follow-up time ranging from 3months to 4years, it was observed a statistically significant reduction in BMI (MD - 8.56kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids

Weight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of weight-loss maintenance. Here, we profile energy-balance-regulating metabokines and sphingolipids in adults with obesity undergoing an initial low-calorie diet-induced weight loss and a subsequent weight-loss maintenance phase with exercise, glucagon-like peptide-1 (GLP-1) analog therapy, both combined, or placebo. We show that circulating growth differentiation factor 15 (GDF15) and C16:0-C18:0 ceramides transiently increase upon initial diet-induced weight loss. Conversely, circulating fibroblast growth factor 21 (FGF21) is downregulated following weight-loss maintenance with combined exercise and GLP-1 analog therapy, coinciding with increased adiponectin, decreased leptin, and overall decrements in ceramide and sphingosine-1-phosphate levels. Subgroup analyses reveal differential alterations in FGF21-adiponectin-leptin-sphingolipids between weight maintainers and regainers. Clinically, cardiometabolic health outcomes associate with selective metabokine-sphingolipid remodeling signatures. Collectively, our findings indicate distinct FGF21, GDF15, and ceramide responses to diverse phases of weight change and suggest that weight-loss maintenance involves alterations within the metabokine-sphingolipid axis.

Comment on Salazar et al. Weight Regain after Metabolic Surgery: Beyond the Surgical Failure. J. Clin. Med. 2024, 13, 1143.

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Weight Loss Failure Post-Bariatric Surgery

Bariatric surgery (BS) is the most effective intervention for obesity, with proven significant weight loss, complications prevention, comorbidity remission, and improved survival. However, a substantial proportion of patients experience weight loss failure after BS. This review aims to provide an updated insight into weight loss failure after BS, define it, identify its prevalence, explain its health impact, determine risk factors, and summarize prevention and treatment. Future directives and larger-scale prospective studies should be considered to define weight regain (WR) and insufficient weight loss post bariatric surgery and address measures to resolve gaps and controversies.