Long-term Weight Loss Research Articles

Effects of Women's Body Satisfaction, Emotional Eating, and Race on Short-, Mid-, and Long-term Weight Loss

ObjectiveTo improve understanding of psychosocial factors, their changes, and racial differences with implications for behavioral obesity treatments. MethodsWomen with obesity of White (n = 64) and Black (n = 33) racial groups participated in cognitive-behavioral community-based obesity treatment and were assessed on body satisfaction, emotional eating, and weight changes over 3, 6, 12, and 24 months via mixed-model repeated-measures analysis of variance and stepwise multiple regression analyses. ResultsBaseline body satisfaction scores were significantly higher (P < 0.001) in Black participants. White participants had significantly higher (P = 0.04) emotional eating scores. Significant overall improvements (P < 0.001) in body satisfaction, emotional eating, and weight were found, with weight reduction significantly greater (P = 0.05) among the White women. Weight reductions were significantly predicted by changes in body satisfaction and emotional eating (R2 = 0.12–0.20, P < 0.01). When racial group was entered into the analyses, the explained variance in weight change over 6 and 12 months significantly increased (P < 0.05). Conclusions and ImplicationsFindings suggest addressing body satisfaction, emotional eating, and racial differences by adjusting obesity treatment targets could improve outcomes. Research-to-practice needs include a control group and further identification/elucidation of other psychosocial and economic factors that might affect outcomes.

Impact of 4-week of a restricted Mediterranean diet on taste perception, anthropometric, and blood parameters in subjects with severe obesity.

The study of taste functionality and its relation to human health is receiving growing attention. Obesity has been reported to cause alterations in sensory perception regarding system functionality and preferences. However, a small body of research addresses tastes perception and its modification with the achievement of body mass reduction through surgical intervention. Much fewer efforts have been made to evaluate the impact of mild restrictive nutritional intervention on gustatory functions. Thus, the objectives of this study were to determine if a dietary intervention of 4 weeks following a restricted balanced Mediterranean diet would affect the sweet and salty taste thresholds of subjects with severe obesity and could influence their anthropometric and blood parameters. Fifty-one patients with severe obesity (F: 31; age: 43.7 ± 12.5; BMI = 47.6 ± 1.0) were enrolled in the study. The recognition threshold for sweet and salty taste and anthropometric and blood parameters were assessed before and after the 4-week weight loss program. The Mediterranean diet has proven to be an effective treatment, significantly improving all anthropometric and blood parameters (p < 0.05) after 4 weeks of intervention. Moreover, the hypo-sodium treatment associated with the diet significantly improved the salty threshold (p < 0.001). No changes were detected for the sweet threshold. Collectively, these data highlight that dietary treatment might impact taste perception differently. Therefore, a taste-oriented nutritional intervention could represent a novel approach to developing more individualized, taste-oriented follow-up interventions to maintain sustainable and long-term weight loss.

Examining differences in long-term weight loss outcomes after bariatric surgery: The role of romantic relationship status.

This study tested for differences based on relationship status at the time of surgery in baseline body mass index (BMI), weight loss outcomes (change in BMI [ΔBMI], percent total weight loss [%TWL], percent excess weight loss [%EWL]), and rates of successful weight loss (defined as ≥ 50%EWL) up to 4-year postbariatric surgery. Data came from a secondary analysis of patients (N = 492) who were up to 4-year postsurgery and completed a presurgical psychological evaluation and postsurgical survey. Sixty-nine percent of participants were patients in committed relationships and 31% were single/divorced/widowed patients. Single patients had higher presurgical BMIs than those who were partnered (t = 2.28, p = .02). There were no differences between those who were partnered and singles regarding ΔBMI and %TWL, although singles had smaller %EWL (t = -2.08, p = .04), which became nonsignificant after controlling for covariates. Most participants had successful weight loss (76.8%); however, this was not related to romantic relationship status. The results suggest those who were partnered undergo surgery at better-starting weights than singles and maintain this advantage in the long term. Providers working with patients considering bariatric surgery could inquire about how their romantic and social relationships play a part in their decision-making process. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Bariatric surgery alters mitochondrial function in gut mucosa.

The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria-a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS. Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content. Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups. Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes.

Long-Term Outcome of Laparoscopic Sleeve Gastrectomy (LSG) on Weight Loss in Patients with Obesity: a 5-Year and 11-Year Follow-Up Study

BackgroundBariatric surgery is the most efficient treatment for patients with clinically severe obesity who have failed to obtain satisfactory weight loss through lifestyle modification and medical treatments. This study aimed to present our long-term laparoscopic sleeve gastrectomy (LSG) efficacy in terms of weight loss and obesity-related complications resolution.Patients and MethodsThis is a retrospective study that was based on prospectively collected data from patients undergoing LSG by the same surgeon from July 2011 to the end of August 2022. The LSG-associated short-term (at 3 months, 6 months, and 1 year postoperatively) and long-term (at 5 years and 11 years postoperatively) weight loss, and the short-term (6 months postoperatively) and long-term (5 and 11 years postoperatively) rates of obesity-related complications were assessed.ResultsThis study included 892 patients who underwent LSG over 11 years. At the 1-year follow-up, data on 860 patients were available, while at the 5-year and 11-year follow-ups, data on 193 patients and 48 patients, respectively, were available. The mean EBWL% was 84.57 ± 18.41%, 64.22 ± 15.53%, and 66.01 ± 8.66% at the 1-year, 5-year, and 11-year follow-ups, respectively.ConclusionThis study adds new evidence concerning the short-term efficacy of LSG. The long-term assessment showed relatively sustainable weight loss and obesity-related complications resolution, with a regression of the short-term gains that was still far from the baseline burden.Graphical

A Review of the Anti-Obesity Effects of Wild Edible Plants in the Mediterranean Diet and Their Active Compounds: From Traditional Uses to Action Mechanisms and Therapeutic Targets.

Obesity is a long-term condition resulting from a continuous imbalance between the amount of energy consumed and expended. It is associated with premature mortality and contributes to a large portion of the global chronic disease burden, including diabesity, cardiovascular disease, hypertension, and some cancers. While lifestyle changes and dietary adjustments are the primary ways to manage obesity, they may not always be sufficient for long-term weight loss. In these cases, medication may be necessary. However, the options for drugs are limited due to their potential side effects. As a result, there is a need to identify safe and effective alternative treatments. Recently, dietary compounds, plants, and bioactive phytochemicals have been considered as promising sources for discovering new pharmacological agents to treat obesity and its related complications. These natural products can function independently or synergistically with other plants to augment their effects at various levels of the body. They can modulate appetite, lipase activity, thermogenesis and fat synthesis and degradation, satiation, adipogenesis, and adipocyte apoptosis. Additionally, targeting adipocyte growth and differentiation with diverse medicinal plants/diet is a significant strategy for devising new anti-obesity drugs that can intervene in preadipocytes, maturing preadipocytes, and mature adipocytes. Clinical trials have shown that the wild edible plants in the Mediterranean diet can reduce the risk of obesity and its related diseases. This review examines the effectiveness of the common components of the Mediterranean diet in managing obesity and its associated health issues. We conducted a comprehensive literature review using PubMed, Science Direct, Google Scholar, and Medline Plus to gather data on the therapeutic effects of the Mediterranean diet and phytochemicals in treating obesity and its associated diseases.

Management of children with obesity at local hospital and impact of COVID-19 pandemic.

This study investigated the status of children with obesity before and after the COVID-19 pandemic, and the effects of lifestyle guidance on weight loss among children in Japan. We analysed the data of patients who visited our hospital after check-ups for obesity and evaluated the efficacy of lifestyle guidance. The patients were divided into groups A, B, and C (year 2011, 2019, and 2021, respectively). There were no differences in body weight, obesity index (OI), blood pressure, or alanine transaminase (ALT) levels between the groups; however, aspartate transaminase (AST) level was the highest in Group C. In Group C, only OI increased between the primary and secondary screenings; however, OI and body mass index (BMI) improved during the second screening and more children in the weight loss group followed lifestyle guidance. OI/BMI did not change over the past decade; however, short-term weight gain was significant owing to the COVID-19 pandemic, and simple guidance was effective in reducing weight. Future challenges include identifying methods to achieve long-term weight loss.

Initial weight loss and early intervention adherence predict long-term weight loss during the Promoting Successful Weight Loss in Primary Care in Louisiana lifestyle intervention.

This study tested whether initial weight change (WC), self-weighing, and adherence to the expected WC trajectory predict longer-term WC in an underserved primary-care population with obesity. Data from the intervention group (n = 452; 88% women; 74% Black; BMI 37.3 kg/m2 [SD: 4.6]) of the Promoting Successful Weight Loss in Primary Care in Louisiana trial were analyzed. Initial (2-, 4-, and 8-week) percentage WC was calculated from baseline clinic weights and daily at-home weights. Weights were considered adherent if they were on the expected WC trajectory (10% at 6 months with lower [7.5%] and upper [12.5%] bounds). Linear mixed-effects models tested whether initial WC and the number of daily and adherent weights predicted WC at 6, 12, and 24 months. Percentage WC during the initial 2, 4, and 8 weeks predicted percentage WC at 6 (R2 = 0.15, R2 = 0.28, and R2 = 0.50), 12 (R2 = 0.11, R2 = 0.19, and R2 = 0.32), and 24 (R2 = 0.09, R2 = 0.11, and R2 = 0.16) months (all p < 0.01). Initial daily and adherent weights were significantly associated with WC as individual predictors, but they only marginally improved predictions beyond initial weight loss alone in multivariable models. These results highlight the importance of initial WC for predicting long-term WC and show that self-weighing and adherence to the expected WC trajectory can improve WC prediction.

Long-term weight loss as a predictor of mortality in haemodialysis patients.

Serial weight decrease can be a prognostic predictor in chronic haemodialysis (HD) patients. We investigated the impact of long-term post-HD body weight (BW) changes on all-cause mortality among HD patients. This longitudinal cohort study and post-hoc analysis evaluated participants of a previous randomised controlled trial conducted between 2006 and 2011 who were followed up until 2018. Weight change slopes were generated with repeated measurements every 6 months during the trial for patients having ≥5 BW measurements. Participants were categorised into four groups based on quartiles of weight change slopes; the median weight changes per 6 months were -1.02 kg, -0.25 kg, +0.26 kg, and +0.86 kg. Cox proportional hazard regression was used to evaluate differences in subsequent survival among the four groups. BW trajectories were plotted with a backward time-scale and multilevel regression analysis to visualise the difference in BW trajectories between survivors and non-survivors. Among the 461 patients, 404 were evaluated, and 168 (41.6%) died within a median follow-up period of 10.2 years. The Cox proportional hazard regression adjusted for covariates and baseline BW showed that a higher rate of weight loss was associated with higher mortality. The hazard ratios were 2.02 (1.28-3.20), 1.77 (1.10-2.85), 1.00 (reference), and 1.11 (0.67-1.83) for the first, second, third (reference), and fourth quartiles, respectively. BW trajectories revealed a significant decrease in BW in non-survivors. Weight loss elucidated by serial BW measurements every 6 months is significantly associated with higher mortality among HD patients.

The remote diet intervention to reduce Long COVID symptoms trial (ReDIRECT): protocol for a randomised controlled trial to determine the effectiveness and cost-effectiveness of a remotely delivered supported weight management programme for people with Long COVID and excess weight, with personalised improvement goals.

The Remote Diet Intervention to Reduce Long COVID Symptoms Trial (ReDIRECT) evaluates whether the digitally delivered, evidence-based, cost-effective Counterweight-Plus weight management programme improves symptoms of Long COVID in people with overweight/obesity. Baseline randomised, non-blinded design with 240 participants allocated in a 1:1 ratio either to continue usual care or to add the remotely delivered Counterweight-Plus weight management programme, which includes a Counterweight dietitian supported delivery of 12 weeks total diet replacement, food reintroduction, and long-term weight loss maintenance. Randomisation is achieved by accessing a web-based randomisation system incorporated into the study web portal developed by a registered Clinical Trials Unit. We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months. Participants in the control arm enter the weight management programme after six months. We are recruiting participants from social media and existing networks (e.g., Long COVID Scotland groups), through newspaper advertisements and from primary care. Main inclusion criteria: people with Long COVID symptoms persisting > three months, aged 18 years or above, body mass index (BMI) above 27kg/m 2 (>25kg/m 2 for South Asians). The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses). The recruitment for this study started in December 2021 and ended in July 2022. Project results are not yet available and will be shared via peer-reviewed publication once the six-months outcomes have been analysed. Current Controlled Trials ISRCTN12595520.

Long-term weight loss maintenance in females after participation in a community weight management programme – A feasibility study

Long-term weight loss maintenance in females after participation in a community weight management programme – A feasibility study

Longer-Term Weight Loss Outcomes Are Not Primarily Driven by Diet Following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

Metabolic and bariatric surgery (MBS) is the most effective long-term treatment for Class III obesity. Reduced dietary intake is considered a behavioral driver of post-surgical weight loss, but limited data have examined this association. Therefore, this study examined prospective, longitudinal relationships between dietary intake and weight loss over 24 months following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy. Relationships between weight loss and dietary intake were examined using a validated 24-h dietary recall method. Associations between total energy/macronutrient intake and weight loss outcomes were assessed at 12-, 18-, and 24-months following MBS, defining patients as "responders" and "suboptimal responders". Consistent with previous literature, 12-month responders and suboptimal responders showed significant associations between weight loss and energy (p = 0.018), protein (p = 0.002), and total fat intake (p = 0.005). However, this study also revealed that many of these associations are no longer significant 24 months post-MBS (p > 0.05), despite consistent weight loss trends. This study suggests a short-term signal between these dietary factors and weight loss outcomes 12 months post-MBS; however, this signal does not persist beyond 12 months. These results are essential for interpreting and designing clinical studies measuring long-term post-surgical weight loss outcomes.

Clinical outcomes and complications of single anastomosis duodenal-ileal bypass with sleeve gastrectomy: A 2-year follow-up study in Bogotá, Colombia.

The global prevalence of obesity has increased over the past 40 years, and bariatric surgery has proven to be the most effective therapy for long-term weight loss. Its principles are based on modifying the brain-gut axis by altering the gastrointestinal anatomy and affecting the function of gastrointestinal hormones, thereby modifying satiety signals. Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) combines both techniques and has become an alternative to gastric bypass and biliopancreatic diversion procedures for treating severe obesity and associated metabolic diseases in selected patients. To describe the outcomes and complications of SADI-S. We retrospectively analyzed the data of patients who underwent SADI-S laparoscopically at the Clínica Reina Sofía in Bogotá, Colombia. This study assessed the therapeutic effectiveness of SADI-S in terms of short-term preoperative clinical characteristics, postoperative complications, comorbidities, nutritional defi-ciencies, and intraoperative complications during a 2-year follow-up. Sixty-one patients with a mean body mass index (BMI) of 50 ± 7.1 kg/m2 underwent laparoscopic SADI-S. The mean operative time and hospital stays were 143.8 ± 42 min and 2.3 ± 0.8 d, respectively. The mean follow-up period was 18 mo, and the mean BMI decreased to 28.5 ± 12.2 kg/m2. The excess BMI loss was 41.8% ± 13.5%, and the weight loss percentage was 81.1% ± 17.0%. Resolution of obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea, was achieved and defined as complete or partial remission. No intraoperative complications were observed. Short-term complications were observed in four (6.8%) patients. However, larger studies with longer follow-up periods are required to draw definitive conclusions. SADI-S has a low intraoperative and postoperative complication rate and is effective for weight loss and improving obesity-related comorbidities, including hypertension, type 2 diabetes mellitus, dyslipidemia, and sleep apnea syndrome.

Financial toxicity risk among patients with gastric banding complications in the United States: analysis of the National Inpatient Sample

BackgroundLaparoscopic adjustable gastric banding (AGB) was historically among the most performed bariatric procedures but has fallen out of favor in recent years due to poor long-term weight loss and high revisional surgery rates. Significant financial hardship of medical care, known as “financial toxicity,” can occur from experiencing unexpected complications of AGB. ObjectiveTo investigate the risk of financial toxicity among patients being admitted for AGB complications. SettingUnited States. MethodsAll uninsured and privately-insured patients who were admitted for AGB complications were identified from the National Inpatient Sample 2015–2019. Publicly available government data (U.S. Census Bureau, Bureau of Labor, The Centers for Medicare and Medicaid Services) were utilized to estimate patient income, food expenditures, and average maximum out-of-pocket expenditures. Financial toxicity was defined as total admission cost from AGB complications ≥40% of postsubsistence income. ResultsAmong 28,005 patients, 66% patients had private insurance and 44% patients were uninsured. Median total admission cost was $12,443 (interquartile range $7959–$19,859) and $15,182 for those who received revisional bariatric surgery. Approximately 55% of the uninsured patients and 1% of insured patients were at risk of financial toxicity after admission for banding-related complications. Patients who had an emergency admission, revisional surgery, or postoperative intensive care unit admission were more likely to experience financial catastrophe following admission (P < .01). ConclusionsAbout 1 in 2 uninsured patients admitted for AGB-related complications were at risk of financial toxicity. In addition to surgical risks, providers should consider the potential financial consequences of AGB when counselling patients on their choice of surgery.

Future therapies for obesity

Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in multiple obesity-related complications, but it is not scalable at the population level. Over the past few years, gut hormone-based pharmacotherapies for obesity and type 2 diabetes mellitus (T2DM) have rapidly evolved, and combinations of glucagon-like peptide 1 (GLP1) with other gut hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) as dual or triple agonists are under investigation to enhance and complement the effects of GLP1 on WL and obesity-related complications. Tirzepatide, a dual agonist of GLP1 and GIP receptors, marks a new era in obesity pharmacotherapy in which a combination of gut hormones could approach the WL achieved with bariatric surgery. In this review, we discuss emerging obesity treatments with a focus on gut hormone combinations and the concept of a multimodal approach for obesity management.

Five-Year Physical and Psychosocial Outcomes in Obese Adolescents With and Without Metabolic Bariatric Surgery

PurposeMetabolic bariatric surgery (MBS) is increasingly accepted as a treatment for severely obese adolescents. However, its long-term efficacy and safety are not well characterized, particularly in the Eastern Asian population. We aimed to explore the long-term effects of MBS on Chinese adolescents with severe obesity. MethodsA total of 44 obese adolescents (≤18 years old) underwent MBS at our institution from May 2011 to May 2017. A matched nonsurgical control group, including 43 patients, was recruited from lifestyle modification programs in the same period. All patients completed assessments at presurgery/baseline and five years after surgery. The data were collected and analyzed using the χ2 test and an independent sample t-test. ResultsComparing the surgical and control groups revealed that the surgical patients showed significant weight loss and improvement in comorbidities, while the nonsurgical patients showed a trend of weight gain and increased comorbidities (p < .05). Furthermore, the surgical patients had a higher composite physical quality of life (as determined by the Short Form-36 questionnaire). On the other hand, the patients who underwent MBS had a higher risk of malnutrition. DiscussionCompared with nonsurgical patients, severely obese adolescents who undergo MBS exhibit more effective long-term weight loss, remission of comorbidities, and improved quality of life. Furthermore, more attention should be paid to helping adolescents avoid malnutrition after they undergo MBS.

Distinct adaptations of endocrine and cognitive functions may contribute to high variability in long-term weight loss outcome after bariatric surgery

Background: Bariatric surgery has been widely recognized as the most efficient long-term treatment method in severe obesity, yet therapy success shows considerable interindividual variability. Postoperative metabolic adaptations, including improved gut hormone secretion (GLP-1, PYY and ghrelin), and restored executive function may play an explanatory role in weight loss, yet causes for poor success in individual patients remain unknown. This study investigates gut-hormonal and cognitive characteristics in extreme weight loss responders to bariatric surgery. Methods: Patients (n = 47) with high or low excessive weight loss (EWL) at least 2 years after Roux-en-Y-gastric bypass or sleeve gastrectomy were allocated into good responders (GR, EWL 82.4 ± 11.6%) and poor responders (PR, EWL 24.0 ± SD 12.8%) to study differences in postprandial secretion of GLP-1, PYY, ghrelin and in working memory (WM). Results: Mean BMI was 47.1 ± 6.2 kg/m² in PR (n = 21) and 28.9 ± 3.1 kg/m² in GR (n = 26, p < 0.001). Fasted GLP-1 and PYY were comparable for GR and PR (p > 0.2) and increased strongly after a standardized test meal (300 kcal liquid meal) with a peak at 15 to 30 min. The increase was stronger in GR compared to PR (GLP-1, PYY: Time x Group p < 0.05). Plasma ghrelin levels already differed between groups at fasted state, showing significantly higher levels for GR (p < 0.05). Postprandially, ghrelin secretion was suppressed in both groups, but suppression was higher in GR (Time x Group p < 0.05). GR showed significantly higher WM scores than PR (p < 0.05). Postprandial ghrelin (iAUC), but not GLP-1 or PYY plasma levels, significantly mediated the relationship between EWL and a WM subscore (IS score, CI = 0.07 - 1.68), but not WM main score (MIS score, CI = -0.07 - 1.54), in mediation analyses. Conclusion: Excess weight loss success after bariatric surgical procedures is associated with distinct profiles of gut-hormones at fasted and postprandial state, and differences in working memory. Better working memory performance in GR might be mediated by higher postprandial reduction in ghrelin plasma levels. Future studies need to integrate longitudinal data, larger samples and more sensitive cognitive tests.

Exploring Approved Medications and the Promise of Phase 3 Clinical Trials: Anti-Obesity Drugs in the Sky and on the Horizon.

Obesity is a prevalent global health issue affecting approximately half of the world's population. Extensive scientific research highlights the urgent need for effective obesity management to mitigate health risks and prevent complications. While bariatric surgery has proven to be highly effective, providing substantial short-term and long-term weight loss and resolution of obesity-related comorbidities, it is important to recognize its limitations and associated risks. Given the global obesity epidemic and the limitations of surgical interventions, there is high demand for effective and safe anti-obesity medications (AOMs). In Korea, the Korean Society for the Study of Obesity strongly advocates for the use of pharmacotherapy in Korean adults with a body mass index of 25 kg/m2 or higher who have not achieved weight reduction through non-pharmacological treatments. Currently, five AOMs have been approved for long-term weight management: orlistat, naltrexone/bupropion, phentermine/topiramate, liraglutide, and semaglutide. Tirzepatide is awaiting approval, and compounds such as CagriSema (Novo Nordisk) and oral semaglutide are currently undergoing rigorous evaluation in phase 3 clinical trials. Furthermore, other promising drugs, including orforglipron, BI 456906, and retartrutide, are progressing to phase 3 studies, expanding the therapeutic options for obesity management. In personalized patient care, physicians play a crucial role in accurately identifying individuals who genuinely require pharmacotherapy and selecting appropriate AOMs based on individual patient characteristics. By integrating evidence-based interventions and considering the unique needs of patients, healthcare professionals significantly contribute to the success of obesity management strategies.

373-OR: Repetitive Transcranial Magnetic Stimulation—A Potential Antiobesity Approach for Long-Term Maintenance of Weight Loss

Current anti-obesity interventions result in early rapid weight loss, but long-term maintenance of lost weight is much more challenging. Initial weight loss is typically followed by a weight plateau and progressive regain. We demonstrated the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in inducing long-term weight loss (up to 1 year) in individuals with obesity by modulating the brain dopaminergic system and the prefrontal cortex. In a post-hoc analysis, we re-evaluated body weight loss up to 3 years after, in 44 individuals treated with a 5-week high frequency rTMS or sham stimulation, for obesity. Out of 44 subjects, 30 individuals (21 F/9 M, BMI 35.3±2.8, age 49.9±9.3) did not undergo any further weight loss treatments (except diet), 9 subjects (5 F/4 M, BMI 40.4±4.7, age 44.7±.6.1) underwent bariatric surgery, and 5 patients were treated for persistent obesity with a GLP-1 receptor agonist (GLP1-RA) (5 F/0 M, BMI 36.8±6.5, age 53.2±13.9). Out of 30 subject who did not undergo any further weight loss intervention, the 16 patients who received real rTMS (10 F/6 M, BMI 34.6±3.2, age 49.2±7.5) reported a significant body weight loss compared to the Sham group (11 F/3M, BMI 36.1±2.0, age 50.7±2.0) at the end of the 5-week intervention (BMI:-4.5±1.7% vs -1.6±1.8%, p=0.0001). Crucially, they continued to lose body weight compared to the Sham even 3 years after the end of intervention (BMI: -9.5±7.6% vs -3.6±8.4%, p=0.056). As expected, during the 3-year follow-up, bariatric surgery was more effective in promoting weight loss compared to the rTMS and the GLP1-RA (p=0.0001), but rTMS has not been shown to be less effective than GLP1-RA in maintaining lost weight (p=0.621). This preliminary evidence of efficacy of rTMS in promoting long-term weight loss (over one year) may be explained via neuronal neuroplasticity. TMS alone or in combination with other anti-obesity approaches may open new ways to sustain the efficacy of weight control interventions. Disclosure A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. D.Cannavaro: None. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis. Funding IRCCS MultiMedica (Ricerca Corrente)

1479-P: Targeted Exome Sequencing for Long-Term Efficacy and Weight Loss of Dulaglutide in Type 2 Diabetes

Introduction: There are individual differences in glucose lowering effect and weight reduction of dulaglutide, long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is expected that genetic variations in the mechanism of action of drugs are involved in treatment response to drugs. This study aims to investigate genetic variants associated with long-term efficacy and weight reduction of dulaglutide using targeted next-generation sequencing. Methods: We recruited 77 patients those who were treated with dulaglutide at least one year after switching from DPP-4 inhibitors (±basal insulin) due to uncontrolled type 2 diabetes (HbA1c ≥8.0%) at Korean VHS medical center between September 2018 and October 2019, and followed up until March 2021. The responder was defined by ≥1.0% HbA1c reduction at 24 weeks and achievement of HbA1c ≤7.5% at 52 weeks. We designed targeted exome panel based on the mechanism of drug action, and candidate genetic variants included known GLP-1 response related genes (n=10), gastric emptying related genes (n=18), pancreatic insulin secretion related genes (n=25). At the same time, we also performed whole exome sequencing. Results: During follow-up period of median 2.5±1.3 years, HbA1c was 9.7±1.3% at baseline and reduced to 8.2±1.5% at 6 months, and maintained thereafter up to 4 years. Glycemic response was associated with GNB3, SPARC, and COL4A1 genes. Weight loss (n=13) was more frequently observed in patients with minor G alleles of COL4A1 gene (OR 2.516, 95% CI 1.013, 6.249, p=0.047). Glycemic effectiveness of dulaglutide therapy is associated with genetic variants (OR 2.106, 95% CI 1.358, 3.265, p=0.001) as well as baseline HbA1c (OR 1.682, 95% CI 1.067, 2.650, p=0.025). Conclusion: The glucose lowering effect of dulaglutide, which exempts some patients from insulin therapy, has been associated with GNB3, SPARC, and COL4A1 variants. Polymorphisms in COL4A1 gene was associated with weight loss, although further studies are needed for validation. Disclosure Y.Kim: None. J.Seo: None. Funding VHS Medical Center (VHSMC20026)