Metabolism open最新文献

{"title":"Efficacy of Momordica charantia in glycaemic control and insulin resistance among patients with prediabetes and type 2 diabetes. A GRADE-adherent meta-analysis of randomised controlled trials","authors":"Sphesihle A.L. Mkhize ,&nbsp;Wendy N. Phoswa ,&nbsp;Phikelelani S. Ngubane ,&nbsp;Kabelo Mokgalaboni","doi":"10.1016/j.metop.2025.100407","DOIUrl":"10.1016/j.metop.2025.100407","url":null,"abstract":"<div><div>The prevalence of prediabetes is rising globally, and if untreated, it can lead to a surge in the rate of type 2 diabetes (T2D). Altogether, these conditions are characterised by hyperglycaemia, which promotes cardiovascular complications. Although Momordica has shown promising results in preclinical studies, the existing quantitative synthesis of evidence reports contradictory findings. This study aimed to evaluate the effect of <em>Momordica charantia</em> on fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, homeostatic model of insulin resistance (HOMA-IR), and homeostatic model of β-cell function (HOMA-β) in individuals with prediabetes or T2D. A search for randomised controlled trials was conducted on Scopus, PubMed, and Web of Science until July 19, 2025. Keywords used included <em>M. charantia</em>, bitter melon, prediabetes and diabetes mellitus. The data were presented as standard mean difference (SMD) and 95 % confidence intervals. Twenty-five trials with 34 sub-studies were deemed relevant. The results showed reduced FBG [SMD = −0.46 (−0.73, - 0.18), <em>p</em> = 0.0012] and HbA1c [SMD = −0.57 (−0.83, −0.31), <em>p</em> &lt; 0.0001]. Additionally, there was a significant reduction in the level of insulin [SMD = −0.48 (−0.83, −0.12), <em>p</em> = 0.0082] and HOMA-IR [SMD = −0.52 (−0.95, −0.08), <em>p</em> = 0.0195]. However, no effect was observed on HOMA-β (<em>p</em> = 0.586). The study findings suggest that <em>M. charantia</em> may be used to improve insulin sensitivity and reduce insulin resistance, thereby improving hyperglycaemia in patients with prediabetes and T2D.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100407"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using metabolic syndrome severity in the “real world”: Associations with diabetes and cardiovascular disease in all of us vs. NHANES","authors":"Mark D. DeBoer ,&nbsp;Matthew J. Gurka ,&nbsp;Marieke K. Jones ,&nbsp;Mark E. Smolkin","doi":"10.1016/j.metop.2025.100415","DOIUrl":"10.1016/j.metop.2025.100415","url":null,"abstract":"<div><h3>Background</h3><div>While the severity of the metabolic syndrome (MetS) is associated with type 2 diabetes and cardiovascular disease (CVD) in research cohorts, it is unclear if this association remains when using clinically-collected data, which is more subject to error and bias.</div></div><div><h3>Methods</h3><div>We used a previously-validated MetS-severity z-score (MetS-Z) to compare the degree of cardiometabolic derangement between clinically-collected data from the electronic health-record (EHR) in the All-of-Us cohort (N = 101,676) with research-collected data from NHANES 2017–2020 (n = 3470). We assessed (separately) the odds of current diabetes and CVD in each cohort based on MetS z-score, adjusted for sex, race/ethnicity, education and income.</div></div><div><h3>Results</h3><div>Mean MetS-Z-scores in All of Us (vs. NHANES) were higher overall (0.41 vs. 0.15), including being slightly higher among those without diabetes (0.03 vs. −0.09) and similar among those with diagnosed diabetes (1.42 vs. 1.50). In All of Us (vs. NHANES) MetS-Z was higher among those without CVD (0.36 vs. 0.10) but similar among those with CVD (0.72 vs. 0.66). Adjusted odds of diagnosed diabetes and CVD based on MetS-Z remained significant when using clinically-collected data in All of Us (diabetes: 3.41 [95 % confidence interval 3.34, 3.49]; CVD: 1.20 [1.18, 1.21]), though not as high as in NHANES (diabetes: 5.83 [4.52, 7.51]; CVD: 1.43 [1.27, 1.61]).</div></div><div><h3>Conclusion</h3><div>While EHR data is limited by selection bias and data accuracy concerns (e.g. lack of fasting laboratory testing), we found overall similar relationships between MetS-severity, diabetes and CVD in EHR-based and research-based cohorts, supporting utility of these data in risk algorithms.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100415"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pancreatic islet macrophages in type 2 diabetes mellitus: from underlying pathological mechanisms to therapeutic target discovery","authors":"Zhongpeng Qiu ,&nbsp;Dejing Shang","doi":"10.1016/j.metop.2025.100418","DOIUrl":"10.1016/j.metop.2025.100418","url":null,"abstract":"<div><div>The pathogenesis of type 2 diabetes mellitus (T2DM) is closely associated with chronic inflammation within the islet microenvironment, where pancreatic islet macrophages serve as central orchestrators of local immune regulation. This review provides a systematic overview of the ontogeny, phenotypic heterogeneity, and functional roles of pancreatic islet macrophages in T2DM pathology. Pancreatic islet macrophages contribute to β-cell proliferation and the maintenance of islet homeostasis through the secretion of various growth factors, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Under conditions of metabolic stress, including lipotoxicity and glucotoxicity, these macrophages are polarized toward a pro-inflammatory phenotype. In this state, they impair β-cell function by releasing inflammatory mediators, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Furthermore, this article discusses potential clinical strategies that target pancreatic islet macrophages—such as anti-inflammatory agents and immunomodulators—highlighting their promise as novel perspectives for precise intervention in T2DM.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100418"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Prevalence of normal weight obesity among adults in Southeast Asia: Insights from a systematic review and meta-analysis” [Metabol. Open 28C (2025) 100416]","authors":"K.G. Sruthi ,&nbsp;C. Aditya ,&nbsp;Paramjot Panda ,&nbsp;Jyoti Ranjan Mohanty ,&nbsp;Manas Ranjan Behera","doi":"10.1016/j.metop.2025.100425","DOIUrl":"10.1016/j.metop.2025.100425","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100425"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and metabolic effects of ketone monoester supplementation: The first simultaneous CKM and CGM study under normal diet and activities","authors":"Toshiya Miyatsu,&nbsp;Connor Tate,&nbsp;Jeremy McAdam,&nbsp;Chandler Massey,&nbsp;Timothy Broderick","doi":"10.1016/j.metop.2025.100411","DOIUrl":"10.1016/j.metop.2025.100411","url":null,"abstract":"<div><div>Exogenous ketone supplementation has gained attention for its potential health and performance benefits, yet its real-world pharmacokinetics and metabolic effects remain underexplored. This study investigated the pharmacokinetics of ketone monoester (KME) supplementation during normal diet and activities, leveraging simultaneous interstitial fluid (ISF) continuous ketone and glucose monitoring (CKM and CGM). In this single-group observational study, twenty healthy adults underwent a 10-day KME supplementation protocol following a 4-day baseline period. Weight-based KME dosing rapidly elevated ISF β-hydroxybutyrate (BHB) levels, peaking within 1 h and sustaining ketosis for approximately 5 h. Exploratory correlational analyses revealed a two-stage influence pattern: larger skeletal/adipose mass slowed and blunted peak BHB levels (<em>r</em> = −.52 to −.63, <em>p</em> = .04–.08), whereas higher habitual activity, better baseline glucose regulation and greater protein intake prolonged BHB elevation and associated glucose-suppression window (<em>r</em> = .47–.58, <em>p</em> = .05–.09). Granger causality analysis confirmed that KME supplementation acutely suppressed ISF glucose, with an initial effect at 5 min and a sustained post-dose suppression phase between 25 and 55 min. Surprisingly, fasting glucose levels increased after 10 days of KME supplementation, suggesting compensatory metabolic adaptation. Additionally, sleep efficiency and quality declined during the intervention phase. These findings highlight the complex metabolic effects of KME use, emphasizing the need for personalized approaches to optimize its benefits. This study demonstrates the feasibility of CKM/CGM for capturing real-time metabolic dynamics and underscores the importance of further research into the physiological implications of exogenous ketone supplementation.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100411"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational diabetes alters prefrontal neurochemistry and disrupts maternal behaviors: Role of Fibrillin-1, serotonin, and TNF-α in rats","authors":"Samira Khayat ,&nbsp;Hamed Fanaei ,&nbsp;Abdolvahed Safarzaei","doi":"10.1016/j.metop.2025.100422","DOIUrl":"10.1016/j.metop.2025.100422","url":null,"abstract":"<div><h3>Objective</h3><div>Gestational diabetes mellitus (GDM) is a metabolic disorder that can impact various aspects of maternal behavior and neurochemical processes. This study aimed to investigate the effects of GDM on FBN1 (fibrillin-1) gene expression, TNF-alpha, serotonin and maternal behavior in rat.</div></div><div><h3>Materials and methods</h3><div>A total of twenty female Wistar rats were randomly divided into two groups: the control group and the gestational diabetes mellitus (GDM) group. The study compared maternal behavior patterns between the GDM and control groups and measured the following in the hippocampus and prefrontal cortex: TNF-α and serotonin levels (via ELISA), and FBN1 mRNA expression (via qRT-PCR).</div></div><div><h3>Results</h3><div>The findings demonstrated that TNF-α levels (<em>P</em> = 0.0025) were significantly higher in the prefrontal cortex of the GDM group compared to the control group, whereas serotonin levels (<em>P</em> = 0.0037) were significantly lower. Additionally, <em>FBN1</em> mRNA expression levels (<em>P</em> = 0.012) in the prefrontal cortex of GDM group were significantly higher than those in the control group. In terms of maternal behavior, the GDM group exhibited weakened behaviors compared to the control group. Specifically, endurance of maternal behaviors such as the duration of breastfeeding (P = 0.024), nesting (P = 0.016), and pup grooming (P = 0.017) were significantly decreased in the GDM group compared to control group. The speed of integration of maternal behaviors, specifically the latency to onset of pup retrieval (P = 0.0018), significantly increased, while the number of breastfeeding instances (P = 0.0026) significantly decreased in the GDM group compared to the control group. Furthermore, the emotionality (self-calming) aspect of maternal behavior, specifically self-grooming, exhibited a significant decreases in both duration (P = 0.0097) and number of instances (P = 0.0029) in the GDM group compared to the control group. In the hippocampus, only TNF-α levels were significantly elevated in the GDM group (P = 0.0003); no significant differences were found in serotonin or FBN1 mRNA expression.</div></div><div><h3>Conclusion</h3><div>These results demonstrate that GDM significantly dysregulates prefrontal cortex neurochemistry (increasing TNF-α and FBN1 mRNA while decreasing serotonin) and profoundly weakens maternal behavior, affecting its endurance, speed of integration, and emotional components in rats.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100422"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lysosomal surveillance response promotes healthspan in C. elegans","authors":"Liaoyuan Zheng ,&nbsp;Junli Liu","doi":"10.1016/j.metop.2025.100396","DOIUrl":"10.1016/j.metop.2025.100396","url":null,"abstract":"<div><div>Lysosomes, the cellular recycling hubs, are indispensable for maintaining homeostasis by degrading misfolded proteins, damaged organelles, and foreign pathogens. Their dysfunction is a hallmark of aging and age-related neurodegenerative diseases, where impaired clearance of toxic protein aggregates drives pathogenesis. Nevertheless, the mechanisms by which lysosomal function can be enhanced to mitigate these detrimental processes remain inadequately understood. A recent study conducted by Li et al. describes a newly identified transcriptional program, the Lysosomal Surveillance Response (LySR), that, when activated, significantly extends healthspan and reduces proteotoxicity in <em>C. elegans</em>. This adaptive transcriptional program, governed by the GATA transcription factor, ELT-2, and modulated by the acetyltransferase CBP-1, operates independently of canonical longevity pathways such as the DAF-2 insulin-like signaling. This work not only unveils a previously unrecognized longevity pathway but also charts a new course for developing therapies targeting aging and neurodegeneration.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100396"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of normal weight obesity among adults in Southeast Asia: Insights from a systematic review and meta-analysis","authors":"K.G. Sruthi ,&nbsp;C. Aditya ,&nbsp;Paramjot Panda ,&nbsp;Jyoti Ranjan Mohanty ,&nbsp;Manas Ranjan Behera","doi":"10.1016/j.metop.2025.100416","DOIUrl":"10.1016/j.metop.2025.100416","url":null,"abstract":"<div><h3>Background</h3><div>Normal Weight Obesity (NWO) describes individuals with a normal body mass index (BMI) but elevated body fat percentage (BF%), placing them at increased risk for cardiometabolic complications. This condition is particularly relevant in Southeast Asian populations, where visceral adiposity occurs at lower BMI thresholds. However, regional pooled prevalence data are limited.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in PubMed, EMBASE, Scopus, Web of Science, and Google Scholar for studies published between January 2010 and May 2025. Eligible studies included observational data on adults (≥18 years) from Southeast Asia reporting NWO prevalence, defined by normal BMI (18.5–24.9 kg/m²) with validated surrogate indices indicative of excess adiposity. Two reviewers independently conducted screening, data extraction, and quality appraisal using the Joanna Briggs Institute (JBI) tool. A random-effects meta-analysis was performed using the Freeman-Tukey double arcsine transformation, with heterogeneity assessed via the I² statistic.</div></div><div><h3>Results</h3><div>Eight studies involving 9028 participants from five Southeast Asian countries (Philippines, Malaysia, Thailand, Myanmar, Singapore) were included. The pooled prevalence of NWO was 57 % (95 % CI: 37 %–75 %), with study-specific estimates ranging from 22.8 % to 82 %. Heterogeneity was high (I² = 98.9 %). Most studies used bioelectrical impedance analysis (BIA) for body fat assessment and were rated as moderate to high quality.</div></div><div><h3>Conclusion</h3><div>NWO is common among adults in Southeast Asia, especially in women and young adults. These findings highlight the limitations of BMI as a screening tool and support the integration of body fat assessments into public health screening and clinical protocols for early risk detection.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100416"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver transplantation in the era of obesity: A metabolic public health crisis meets a surgical frontier","authors":"Sofia Rozani ,&nbsp;Maria Dalamaga ,&nbsp;Georg Weber ,&nbsp;Robert Grützmann","doi":"10.1016/j.metop.2025.100410","DOIUrl":"10.1016/j.metop.2025.100410","url":null,"abstract":"<div><div>The global obesity epidemic has reshaped the landscape of liver transplantation (LT). Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the leading indications for LT in Western countries, while excess adiposity simultaneously complicates donor and recipient selection, surgical outcomes, and long-term graft survival. Although previous studies have examined obesity, MASLD, and LT separately, an integrative overview of their bidirectional relationship and its clinical implications is lacking. This mini-review addresses that gap by synthesizing current evidence on how obesity influences LT candidacy, perioperative risk, graft outcomes, and metabolic complications after transplantation. We further highlight emerging concepts of “metabolic fitness,” the role of prehabilitation, novel pharmacotherapies, and bariatric interventions, while underscoring the urgent need for transplant-specific metabolic guidelines. Without upstream prevention and coordinated system-level adaptation, transplant programs will face an unsustainable burden of obesity-related liver disease.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100410"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic target trial emulation and predictive modeling of amylin-pathway therapies for obesity and type 2 diabetes","authors":"Faisal A. Al-Harbi ,&nbsp;Ahmed K. Alsaif ,&nbsp;Atheer G. Almutairi ,&nbsp;Hussam J. Alshehri ,&nbsp;Elan A. Aleidan ,&nbsp;Ghaida S. Alabdulaaly ,&nbsp;Mashael E. Alanazi ,&nbsp;Ahmed Y. Azzam","doi":"10.1016/j.metop.2025.100414","DOIUrl":"10.1016/j.metop.2025.100414","url":null,"abstract":"<div><h3>Introduction</h3><div>Amylin-pathway therapies represent a novel therapeutic class for obesity and type 2 diabetes, however head-to-head comparative data and long-term outcome predictions remain limited. We conducted target trial emulation and computational predictive modeling aiming to predict future trial outcomes and comparative effectiveness across the amylin-pathway development program.</div></div><div><h3>Methods</h3><div>Following PRISMA 2020 and TARGET framework guidelines, we search in the current literature for eligible trials and extracted data from seven randomized controlled trials (N = 5,786 participants) of amylin-pathway therapies published up to September 2025. We reconstructed high-precision synthetic individual patient data (IPD) and developed computational models for virtual head-to-head comparisons, dose-response optimization, longitudinal trajectory prediction, and trial simulation. Network meta-analysis integrated evidence across CagriSema, cagrilintide, and amycretin formulations.</div></div><div><h3>Results</h3><div>Synthetic IPD reconstruction achieved &gt;99 % fidelity to source trials, validated through leave-trial-out cross-validation (efficacy RMSE: 2.9 % points, calibration slope: 0.61; discontinuation RMSE: 0.18, slope: 1.08). Virtual head-to-head modeling confirmed CagriSema superiority over amycretin subcutaneous at matched timepoints (posterior probability &gt;0.95). Dose-response modeling identified optimal amycretin exposures (ED80: 8.88 mg subcutaneous, 95 % CI: 7.12–11.08), with benefit-risk frontier analysis delineating a therapeutic window at 10–20 mg balancing efficacy plateau against tolerability thresholds (GI-AE &lt;75 %, discontinuation &lt;20 %). Longitudinal kinetics showed plateau timing at 52–68 weeks for obesity outcomes and 24–32 weeks for glycemic endpoints. Heterogeneity analysis revealed complete resolution for GI adverse events (I²_DL = 0 %, τ² = 0) and moderate variation for discontinuation (I²_DL = 13 %, τ² = 0.03) after logit-scale correction with proper within-arm variance weighting. Machine learning models predicted treatment response with 82–87 % accuracy using baseline characteristics.</div></div><div><h3>Conclusions</h3><div>Synthetic target trial emulation with structured validation (leave-trial-out, posterior predictive checks, simulation-based calibration) demonstrated promising evidence for amylin-pathway development optimization. Benefit-risk frontier analysis identified an optimal 10–20 mg subcutaneous therapeutic window, and heterogeneity quantification through maximum a posteriori (MAP) predictive interval provides design-ready estimates for confirmatory trials requiring around 800-1,200 participants per arm for 90 % power.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100414"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}