Hormonal factors behind weight regain (WR) after surgical weight loss remain inadequately understood. Growth/differentiation factor 15 (GDF15) has emerged as a potential therapeutic target in obesity treatment. Cortisol, another stress hormone, has also been associated with weight gain at both low and high circulating concentrations. We aimed to compare meal-stimulated GDF15 and cortisol response in adults with and without WR after sleeve gastrectomy (SG). We hypothesized that GDF15 and cortisol response to meal tolerance test (MTT) will be lower in those with versus without WR after SG.Cross-sectional study comprised 21 adults without diabetes, who underwent SG. WR was defined as 100 × (current weight - nadir)/(preoperative weight - nadir) > 10%. GDF15, cortisol, insulin, glucose, and incretins (total glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) circulating concentrations) were measured during MTT (0-240 min) after 3-6 years post-bariatric surgery.All participants were 48% White, 85% female, with mean (SD) age: 43(10) years, and BMI: 36.2(7.6) kg/m. Compared to the non-WR group (n = 6), the WR group (n = 15) had significantly higher BMI (WR: 38.6 ± 7.6 kg/m, non-WR: 30.3 ± 3.5 kg/m, p = 0.02) and showed lower GDF15 response (WR AUC vs non-WR AUC (116143 ± 13973 vs 185798 ± 38884 ng*min/L, p = 0.047)) and lower cortisol response (WR AUC vs non-WR AUC (3492 ± 210 vs 4880 ± 655 µg*min/dL, p = 0.015)). Incretin response did not differ between the groups.GDF15 and cortisol responses to MTT were lower in those who regained the weight after SG compared to those who did not, suggesting that dysregulation in GDF15 and cortisol response following bariatric surgery.© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Weight regain (WR) after bariatric surgery is common. Several factors involved in WR have been identified, but there has been little research on specific eating habits such as eating snacks rather than regular meals and being a "sweet-eater".To determine whether nutritional status, energy and macronutrient intake, eating behaviors and habits were associated with WR in the postoperative period.We conducted a case-control study of patients who had undergone bariatric surgery. Cases were defined as those patients who gained ≥ 15% of weight in the first two years after surgery and controls as those who gained < 15% of weight. Participants completed a 24-hour dietary recall by phone; weight history was obtained from the medical chart. Logistic regression was used to identify nutritional and behavioral factors significantly related to WR.Fifty-four cases (77% female, 57% had undergone sleeve gastrectomy) and 50 controls (70% female, 58% had undergone Roux-en-Y gastric bypass surgery) participated. Their mean age was 43 and 40 years, respectively. We observed four eating and lifestyle habits independently associated with greater odds of post-surgery WR, namely being a "sweet-eater", a "grazer", sedentarism and consuming more daily calories.Eating more daily calories, being a "sweet-eater", a "grazer", and sedentarism were factors related with a greater risk of regaining weight after surgery.

Weight regain after bariatric surgery occurs in up to a third of patients and reduces treatment-associated health benefits. The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) for treatment of type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains to be defined.This was a single centre retrospective observational study conducted at a Swiss bariatric reference centre. Patients with 6 months of treatment with GLP1-RA, up until November 2021, due to weight regain after bariatric surgery were identified. Data on body weight and relevant clinical parameters were collected before and after 6 months of treatment with GLP1-RA. Data are presented as median (interquartile range).Fifty patients (82% female) were included. Before GLP1-RA treatment (liraglutide, n=29; semaglutide, n=21), weight and BMI were 90.5 kg (83.4, 107.9) and 34.0 kg/m (31.7, 38.7), respectively, with a post-bariatric weight regain of 15.1% (10.6, 22.8) of total body weight and 4.6 kg/m (3.3, 6.2). After 6 months of GLP1-RA treatment, a reduction in weight and BMI of 8.8% (5.2, 11.4) of total body weight and 2.9 kg/m (1.8, 4.0) was observed (P value <0.0001), corresponding to 67.4% (40.4, 92.2) of the weight regain. No serious adverse events were reported.For patients experiencing weight regain after bariatric surgery, two-thirds of the weight regain can be safely lost with GLP1-RA, providing clinicians with a therapeutic option for this clinical challenge, and highlights the need for a large-scale randomized clinical trial.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Glucagon-Like- Peptide-1 (GLP-1) receptor agonist has an emerging role in obesity management. This meta-analysis and systematic review evaluated the effectiveness of GLP-1 receptor agonists in aiding weight loss and enhancing cardiometabolic health in patients with insufficient weight loss (IWL) or weight regain (WR) after bariatric surgery. 

The role of glucagon-like peptide-1 receptor agonists (GLP1-RAs) in patients with weight regain after bariatric surgery remains unclear. The objective of this study was to determine the efficacy and safety of 12 months of GLP1-RA treatment in a real-world patient population with weight regain after bariatric surgery.A single-centre retrospective observational study. Patients with post-bariatric weight regain subsequently treated with GLP1-RA were identified, and the effect on weight after 12 months of treatment was determined. Data are presented as medians (interquartile ranges) or frequencies (%), and Wilcoxon signed-rank tests and Mann-Whitney U tests were used for paired and nonpaired group comparisons, respectively.Forty patients (80% female) were included in the analysis. Liraglutide (3.0 mg, daily subcutaneous injection, n = 22) or semaglutide (1.0 mg, weekly subcutaneous injection, n = 18) was started 74.5 (51.0, 108.3) months after surgery following a weight regain of 14.7 (10.3, 19.6)%. After 12 months of GLP1-RA treatment, a total body weight, BMI, and percentage excess body weight reduction of 10.5 (6.1, 14.7) kg, 3.7 (2.5, 5.3) kg/m, and 41.7 (22.1, 70.5)% were observed, corresponding to a loss of 99.3 (61.0, 135.4)% of the weight regained (P-value < 0.0001). The observed reduction in BMI was significantly lower with liraglutide than with semaglutide, 3.1 (2.0, 4.7) vs. 4.7 (3.7, 6.0) kg/m (P-value = 0.04). Adverse events were reported in 13 (32.5%) patients, all of which were mild and transient.GLP1-RA therapy with liraglutide or semaglutide for 12 months is efficacious and safe for the treatment of weight regain following bariatric surgery.Not applicable.© 2025. The Author(s).

About 15% of patients who undergo adjustable gastric banding (AGB) have difficulty losing weight due to, among other factors, the development or maintenance of binge eating disorder. Topiramate is an anticonvulsive drug with proven good results in controlling binge eating episodes. The objective of this study was to analyze the effect of topiramate in patients with AGB.16 patients with binge eating and inadequate weight loss after AGB were analyzed prospectively for 3 months while receiving topiramate in doses varying from 12.5 to 50 mg per day.There was a mean increase in excess weight loss from 20.4% to 34.1% without the need for band readjustment. 2 patients had intolerance to topiramate and were changed to fluoxetine 40 mg per day.Topiramate may be a useful adjuvant for patients with AGB and binge eating disorder.

Sleeve gastrectomy (SG) is a common bariatric procedure that has been shown to be effective in both the short and long term, but it is not without risks, some of which necessitate revision or redo surgery (RS).GBSR (German Bariatric Surgery Registry) data were evaluated in this multicenter analysis. Short-term results (1-year follow-up) of RS (Re-Sleeve gastrectomy, Roux-en-Y gastric bypass, RYGB, Omega-loop gastric bypass, OLGB, and duodenal switch, DS) following primary SG (n = 27939) were evaluated.Of PSG patients, 7.9% (n=2195) needed revision surgery. Nine hundred ninety-four patients underwent the aforementioned four surgical procedures (95 with R-SG, 665 with RYGB, 141 with OLGB, and 93 DS). Loss of follow-up within 1 year 52.44%. The most common reasons for RS were weight regain and/or a worsening of preexisting comorbidities. Regarding the operating time, R-SG was the shortest of the four procedures, and DS was the longest. In general, there were no significant advantages of one procedure over another in terms of complication incidence in these categories. However, certain complications were seen more often after R-SG and DS than with other redo procedures. There were significant differences in BMI reduction 1 year after surgery (RYGB: 5.9; DS: 10.1; OLGB: 9.1; and R-SG: 9.1; p<0.001). GERD, hypertension, and sleep apnea demonstrated statistically significant comorbidity remission. Diabetes exhibited non-significant differences.According to the findings of our study, all revision surgeries effectively resolved comorbidities, promoted weight loss, and lowered BMI. Due to the disparate outcomes obtained by various methods, this study cannot recommend a particular redo method as the gold standard. Selecting a procedure should consider the redo surgery's aims, the rationale for the revision, the patient's current state, and their medical history.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Combination anti-obesity medications (AOMs) to treat postoperative bariatric surgery weight regain have limited data on their use in the clinical setting. Understanding the optimal treatment protocol in this cohort will maximize weight loss outcomes.A retrospective review of bariatric surgery patients ( = 44) presenting with weight regain at a single academic multidisciplinary obesity center who were prescribed AOM(s) plus intensive lifestyle modification for 12 months.Age: 28-76 years old, 93% female, mean weight 110.2 ± 20.3 kg, BMI 39.7 ± 7.4 kg/m, presenting 5.2 ± 1.6 years post-bariatric surgery [27 (61.4%), 14 (31.8%), and 3 (6.8%) laparoscopic Roux-en-Y gastric bypass (RYGB), laparoscopic vertical sleeve gastrectomy (VSG), and open RYGB, respectively], with 15.1 ± 11.1 kg mean weight gain from nadir. Mean weight loss after medical intervention at 3-, 6-, and 12-month time points was 4.4 ± 4.6 kg, 7.3 ± 7.0 kg, and 10.7 ± 9.2 kg, respectively. At 12 months, individuals prescribed 3 or more AOMs lost more weight than those prescribed one (-14.5 ± 9.0 kg vs. -4.9 ± 5.7 kg,  < 0.05) irrespective of age, gender, number of comorbidities, initial weight or BMI, type of surgery, or GLP1 use. RYGB patients lost less weight overall (7.4% vs. 14.8% VSG respectively;  < 0.05).Combination AOMs may be needed to achieve optimal weight loss results to treat post-operative weight regain.© 2022 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.

Weight loss after pharmacotherapy varies greatly. We aimed to examine associations of quantitative gastrointestinal and psychological traits with obesity, and to validate the ability of these traits to predict responses of obese individuals to pharmacotherapy.In a prospective study, we measured gastric emptying of solids and liquids, fasting and postprandial gastric volume, satiation by nutrient drink test (volume to fullness and maximal tolerated volume), satiety after an ad libitum buffet meal, gastrointestinal hormones, and psychological traits in 328 normal-weight, overweight, or obese adults. We also analyzed data from 181 previously studied adults to assess associations betwecen a subset of traits with body mass index and waist circumference. Latent dimensions associated with overweight or obesity were appraised by principal component analyses. We performed a proof of concept, placebo-controlled trial of extended-release phentermine and topiramate in 24 patients to validate associations between quantitative traits and response to weight-loss therapy.In the prospective study, obesity was associated with fasting gastric volume (P =.03), accelerated gastric emptying (P <.001 for solids and P =.011 for liquids), lower postprandial levels of peptide tyrosine tyrosine (P = .003), and higher postprandial levels of glucagon-like peptide 1 (P <.001). In a combined analysis of data from all studies, obesity was associated with higher volume to fullness (n = 509; P =.038) and satiety with abnormal waist circumference (n = 271; P =.016). Principal component analysis identified latent dimensions that accounted for approximately 81% of the variation among overweight and obese subjects, including satiety or satiation (21%), gastric motility (14%), psychological factors (13%), and gastric sensorimotor factors (11%). The combination of phentermine and topiramate caused significant weight loss, slowed gastric emptying, and decreased calorie intake; weight loss in response to phentermine and topiramate was significantly associated with calorie intake at the prior satiety test.Quantitative traits are associated with high body mass index; they can distinguish obesity phenotypes and, in a proof of concept clinical trial, predicted response to pharmacotherapy for obesity. ClinicalTrials.gov Number: NCT01834404.Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Despite increasing public health concerns regarding obesity, few safe and effective drug treatments are available. Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants.Men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA. Participants were prescribed mild hypocaloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB16), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation. Randomisation was done by use of a centralised, computer-generated, web-based system and was stratified by study centre. Co-primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more. The primary analysis included all randomised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug (last observation carried forward). This study is registered with ClinicalTrials.gov, number NCT00532779.1742 participants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453 (83%) were included in the primary analysis (n=471; n=471; n=511). Mean change in bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone 32 mg plus bupropion group (p<0.0001 vs placebo) and -5.0% (0.3) in the naltrexone 16 mg plus bupropion group (p<0.0001 vs placebo). 84 (16%) participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (p<0.0001 vs placebo) and 186 (39%) assigned to naltrexone 16 mg plus bupropion (p<0.0001 vs placebo). The most frequent adverse event in participants assigned to combination treatment was nausea (naltrexone 32 mg plus bupropion, 171 participants [29.8%]; naltrexone 16 mg plus bupropion, 155 [27.2%]; placebo, 30 [5.3%]). Headache, constipation, dizziness, vomiting, and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group. A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups. Combination treatment was not associated with increased depression or suicidality events compared with placebo.A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity.Orexigen Therapeutics.Copyright 2010 Elsevier Ltd. All rights reserved.