Latest news with #RYGB
Medscape
7 hours ago
- Health
- Medscape
Novel Gene Risk Score Predicts Outcomes After RYGB Surgery
A novel gene risk score, informed by machine learning, predicted weight-loss outcomes after Roux-en-Y gastric bypass (RYGB) surgery, a new analysis showed. The findings suggested that the MyPhenome test (Phenomix Sciences) can help clinicians identify the patients most likely to benefit from bariatric procedures and at a greater risk for long-term weight regain after surgery. 'Patients with both a high genetic risk score and rare mutations in the leptin-melanocortin pathway (LMP) had significantly worse outcomes, maintaining only 4.9% total body weight loss [TBWL] over 15 years compared to up to 24.8% in other genetic groups,' Phenomix Sciences Co-founder Andres Acosta, MD, PhD, told Medscape Medical News . The study included details on the score's development and predictive capability. 'More Precise Bariatric Care' The researchers recently developed a machine learning-assisted gene risk score for calories to satiation (CTSGRS), which mainly involves genes in the LMP. To assess the role of the score with or without LMP gene variants on weight loss and weight recurrence after RYGB, they identified 707 patients with a history of bariatric procedures from the Mayo Clinic Biobank. Patients with duodenal switch, revisional procedures, or who used antiobesity medications or became pregnant during follow-up were excluded. To make predictions for 442 of the patients, the team first collected anthropometric data up to 15 years after RYGB. Then they used a two-step approach: Assessing for monogenic variants in the LMP and defining participants as carriers (LMP+) or noncarriers (LMP-). Then they defined the gene risk score (CTSGRS+ or CTSGRS-). The result was four groups: LMP+/CTSGRS+, LMP+/CTSGRS-, LMP-/CTSGRS+, and LMP-/CTSGRS-. Multiple regression analysis was used to analyze TBWL percentage (TBWL%) between the groups at different timepoints, adjusting for baseline weight, age, and gender. At the 10-year follow-up, the LMP+/CTSGRS+ group demonstrated a significantly higher weight recurrence (regain) of TBW% compared to the other groups. At 15 years post-RYGB, the mean TBWL% for LMP+/CTSGRS+ was -4.9 vs -20.3 for LMP+/CTSGRS-, -18.0 for LMP-/CTSGRS+, and -24.8 for LMP-/CTSGRS-. Further analyses showed that the LMP+/CTSGRS+ group had significantly less weight loss than LMP+/CTSGRS- and LMP-/CTSGRS- groups. Based on the findings, the authors wrote, 'Genotyping patients could improve the implementation of individualized weight-loss interventions, enhance weight-loss outcomes, and/or may explain one of the etiological factors associated with weight recurrence after RYGB.' Acosta noted, 'We're actively expanding our research to include more diverse populations by age, sex, and race. This includes ongoing analysis to understand whether certain demographic or physiological characteristics affect how the test performs, particularly in the context of bariatric surgery.' The team also is investigating the benefits of phenotyping for obesity comorbidities such as heart disease and diabetes, he said, and exploring whether early interventions in high-risk patients can prevent long-term weight regain and improve outcomes. In addition, Acosta said, the team recently launched 'the first prospective, placebo-controlled clinical trial using the MyPhenome test to predict response to semaglutide.' That study is based on earlier findings showing that patients identified with a Hungry Gut phenotype lost nearly twice as much weight on semaglutide compared with those who tested negative. Overall, he concluded, 'These findings open the door to more precise bariatric care. When we understand a patient's biological drivers of obesity, we can make better decisions about the right procedure, follow-up, and long-term support. This moves us away from a one-size-fits-all model to care rooted in each patient's unique biology.' Potentially Paradigm-Shifting Onur Kutlu, MD, associate professor of surgery and director of the Metabolic Surgery and Metabolic Health Program at the Miller School of Medicine, University of Miami, Miami, commented on the study for Medscape Medical News . 'By integrating polygenic risk scores into predictive models, the authors offer an innovative method for identifying patients at elevated risk for weight regain following RYGB.' 'Their findings support the hypothesis that genetic predisposition — particularly involving energy homeostasis pathways — may underlie differential postoperative trajectories,' he said. 'This approach has the potential to shift the paradigm from reactive to proactive management of weight recurrence.' Because current options for treat weight regain are 'suboptimal,' he said, 'prevention becomes paramount. Preoperative identification of high-risk individuals could inform surgical decision-making, enable earlier interventions, and facilitate personalized postoperative monitoring and support.' 'If validated in larger, prospective cohorts, genetic risk stratification could enhance the precision of bariatric care and improve long-term outcomes,' he added. 'Future studies should aim to validate these genetic models across diverse populations and explore how integration of behavioral, psychological, and genetic data may further refine patient selection and care pathways.' The study presented at Digestive Disease Week (DDW) 2025 was funded by Mayo Clinic and Phenomix Sciences. Gila Therapeutics and Phenomix Sciences licensed Acosta's research technologies from the University of Florida and Mayo Clinic. Acosta declared receiving consultant fees in the past 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, BI, Currax, Nestle, Phenomix Sciences, Bausch Health, and RareDiseases, as well as funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, and Rhythm Pharmaceuticals. Kutlu declared having no conflicts of interest.
Yahoo
01-05-2025
- Health
- Yahoo
Amylyx doses first subject in trial of post-bariatric hypoglycaemia treatment
Amylyx Pharmaceuticals has dosed the first subject in the randomised Phase III LUCIDITY trial of glucagon-like peptide-1 (GLP-1) receptor antagonist avexitide for treating post-bariatric hypoglycaemia (PBH). The double-blind, multicentre, placebo-controlled trial aims to assess the safety and efficacy of the therapy in these individuals who have undergone Roux-en-Y gastric bypass (RYGB) surgery. It involves nearly 75 such subjects across 20 sites in the US. The primary endpoint, agreed upon with the US Food and Drug Administration (FDA), focuses on the decrease in the composite of level 2 and level 3 hypoglycaemic events through week 16, with tolerability and safety also under evaluation. This study has inclusion and exclusion criteria similar to previous Phase II studies of the therapy in PBH. Subjects will be randomised in a 3:2 ratio and will be given either 90mg of the therapy once a day subcutaneously or a placebo. Up to six weeks of screening duration will be included in the trial, alongside a three-week run-in period, and a double-blind treatment phase for 16 weeks. Those completing the double-blind phase will be qualified for a 32-week open-label extension period. The current trial was built upon the therapy's five previous trials' data in PBH, which demonstrated the consistent, dose-dependent effects, as well as minimisations in hypoglycaemic events. The safety profile of the therapy is claimed to be favourable and replicated across these trials. Amylyx Pharmaceuticals chief medical officer Camille Bedrosian said: 'With robust data generated to date from five previous clinical trials in PBH, we are excited about the potential for avexitide to address the persistent, recurrent, and debilitating hypoglycaemic events associated with PBH.' Amylyx anticipates that its current cash reserves will sustain operations through the end of 2026. This financial stability is expected to support the completion of recruitment for the LUCIDITY trial by this year, with results anticipated in the first half of 2026. Avexitide has been assessed in five Phase I and II trials for PBH and has also been under investigation for congenital hyperinsulinism (HI). Recently, Amylyx dosed the first subject in the randomised Phase I LUMINA trial, which is assessing AMX0114 as a potential treatment for amyotrophic lateral sclerosis (ALS). "Amylyx doses first subject in trial of post-bariatric hypoglycaemia treatment" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site.
