The Journal of clinical endocrinology and metabolism最新文献

{"title":"Gestational Glucose Intolerance and Risk of Obesity in Childhood and Adolescence.","authors":"Jacqueline Maya, Carolin C M Schulte, Sarah Hsu, Kaitlyn James, Tanayott Thaweethai, Deepti Pant, Marie-France Hivert, Camille E Powe","doi":"10.1210/clinem/dgaf345","DOIUrl":"10.1210/clinem/dgaf345","url":null,"abstract":"<p><strong>Objective: </strong>An association between in utero exposure to gestational glucose intolerance ([GGI], abnormal glucose screening without gestational diabetes), and offspring obesity has not been consistently observed.</p><p><strong>Methods: </strong>In a retrospective cohort, we studied the risk of obesity (body mass index [BMI] > 95th percentile), in 2-5, 6-10, and 11-18-year-olds exposed to varying degrees of maternal glycemia in utero: normal glucose tolerance (NGT), GGI (0 abnormal glucose values, GGI-0, or 1 abnormal value, GGI-1) or gestational diabetes (GDM >2 of 4 abnormal values). We used generalized estimating equations for logistic regression to estimate odds ratios for obesity in each glycemic category compared to NGT, adjusting for maternal age, parity, insurance, race/ethnicity, marital status, infant sex, gestational age, and gestational weight gain. A second model additionally adjusted for maternal 1st trimester BMI.</p><p><strong>Results: </strong>We included 27,876 children and adolescents from 23,334 (83.7%) NGT pregnancies, 3,413 (12.2%) GGI pregnancies, and 1,129 (4.1%) GDM pregnancies. The prevalence of obesity was 13.5% at age 2-5, 20.3% at age 6-10, and 23.4% at age 11-18. Those exposed to GGI-1 and GDM had increased odds of obesity compared to NGT. Adjusting for maternal BMI attenuated this association in all age and glycemic exposure groups, but it remained significantly elevated in 6-10-year-olds exposed to GDM (odds ratio (OR): 1.21, 95%CI [1.01, 1.46] and 11-18-year-olds exposed to GGI-1 and GDM (GGI-1 OR: 1.44 [1.14, 1.81]; GDM OR: 1.28 [1.03, 1.59]).</p><p><strong>Conclusion: </strong>Older children and adolescents exposed to GGI-1 and GDM in utero have a higher risk of obesity than those born to NGT pregnancies, even after accounting for maternal BMI.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289753","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":"Metabolic dysfunction-associated steatotic liver disease alters fatty acid profiles in the liver and adipose tissue.","authors":"Saana Palomurto, Kirsi A Virtanen, Vesa Kärjä, Ursula Schwab, Dorota Kaminska, Pirjo Käkelä, Jussi Pihlajamäki, Ville Männistö","doi":"10.1210/clinem/dgaf346","DOIUrl":"https://doi.org/10.1210/clinem/dgaf346","url":null,"abstract":"<p><strong>Context: </strong>The alterations in systemic fatty acid (FA) metabolism in metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear.</p><p><strong>Objective: </strong>To investigate inter-tissue crosstalk in FA metabolism in patients with MASLD, we compared FA profiles in the liver, serum, visceral, and subcutaneous adipose tissue of patients with severe obesity and normal liver, simple steatosis, or metabolic dysfunction-associated steatohepatitis (MASH).</p><p><strong>Methods: </strong>Preoperative serum, liver, subcutaneous, and visceral adipose tissue samples were collected during laparoscopic gastric bypass surgery from 183 patients with severe obesity patients (122 women, mean age 46.9 ± 9.7 years, body mass index 43.5 ± 5.7 kg/m2). FA composition was analyzed using gas-liquid chromatography. The Kruskal-Wallis test was used to compare the FA proportions in different tissue depots.</p><p><strong>Results: </strong>FA proportions varied more in the liver than in adipose tissue in patients with MASH. Polyunsaturated FAs (PUFA) proportions were significantly lower in the livers of patients with MASH than in those with normal livers (all adjusted P< 0.01). Conversely, dihomo-gamma-linolenic acid, adrenic acid, and arachidonic acid proportions were higher in the adipose tissues of patients with MASH (all adjusted p < 0.001).</p><p><strong>Conclusions: </strong>Patients with MASH exhibited reduced hepatic PUFA content, increased hepatic saturated FAs, and a higher n6-to-n3 PUFA ratio, whereas no clear trends were observed in adipose tissue. These findings highlight distinct differences in FA metabolism between the liver and adipose tissue in MASLD, emphasizing tissue-specific regulatory mechanisms.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278143","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":"Clinical and Genetic Characteristics of Adult Nonautoimmune Hypothyroidism: A Single-Institution Study.","authors":"Chiho Sugisawa, Erika Uehara, Kanako Tanase-Nakao, Kosuke Inoue, Tatsuya Iida, Fumiko Otsuka, Nami Suzuki, Hidemi Ohye, Miho Fukushita, Masako Matsumoto, Ai Yoshihara, Natsuko Watanabe, Kiminori Sugino, Jaeduk Yoshimura Noh, Matsuo Taniyama, Satoshi Narumi, Koichi Ito","doi":"10.1210/clinem/dgaf352","DOIUrl":"https://doi.org/10.1210/clinem/dgaf352","url":null,"abstract":"<p><strong>Purpose: </strong>Nonautoimmune hypothyroidism is characterized by hypothyroidism with negative thyroid autoantibodies with limited knowledge of its clinical and genetic characteristics. The aim was to characterize the clinical and genetic features of nonautoimmune hypothyroidism.</p><p><strong>Methods: </strong>This retrospective study included 1,470 treatment-naive adult hypothyroid patients (serum TSH >10 mU/L) born before 1979 and were followed up at Ito Hospital, Tokyo, Japan. Of them, 220 patients were diagnosed with idiopathic nonautoimmune hypothyroidism by thyroid autoantibody measurements. Sequencing of 13 genes associated with nonautoimmune hypothyroidism was performed of 101 of the 220 patients. Clinical characteristics, including thyroid function and morphology, were systematically evaluated.</p><p><strong>Results: </strong>The proportion of idiopathic nonautoimmune hypothyroidism among the 1,470 patients with treatment-naive non-transient hypothyroidism was 15.0%. Idiopathic nonautoimmune hypothyroidism patients had lower serum TSH (17.0 vs. 28.3 mU/L; P<0.001), higher serum fT4 (11.5 vs. 8.9 pmol/L; P<0.001), and a smaller thyroid volume (13.4 vs. 24.9 g; P<0.001) than autoimmune hypothyroidism patients. Genetic analysis showed that 5.0% of the analyzed idiopathic nonautoimmune hypothyroidism patients had a Mendelian disorder, with PAX8 being the most commonly affected gene. An additional 19% of the analyzed patients carried monoallelic variants in hypothyroidism-associated genes, such as DUOX2, DUOXA2, SLC26A4, TG, TPO, and TSHR, that cause autosomal recessive genetic defects.</p><p><strong>Conclusions: </strong>In patients with treatment-naive adult nonautoimmune hypothyroidism, thyroid dysfunction was milder, and thyroid volume was smaller than in patients with autoimmune hypothyroidism. Mendelian forms were rare, but the unexpectedly high frequency of monoallelic variant carriers suggests that these variants may confer genetic risk for nonautoimmune hypothyroidism.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278141","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":"Multiple or Single Endocrine Abnormalities Associated with Immune Checkpoint Inhibitors.","authors":"Fumika Kamitani, Yuichi Nishioka, Hiroki Nakajima, Yukako Kurematsu, Sadanori Okada, Tomoya Myojin, Tatsuya Noda, Tomoaki Imamura, Yutaka Takahashi","doi":"10.1210/clinem/dgaf347","DOIUrl":"https://doi.org/10.1210/clinem/dgaf347","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are associated with various endocrine abnormalities. However, their underlying pathophysiology remains unclear. We investigated the effect of multiple endocrine abnormalities on the overall survival (OS) of patients treated with ICIs.</p><p><strong>Methods: </strong>In total, 12,978 patients who received ICIs between 2014 and 2022 were investigated using the DeSC Japanese administrative claims database. Endocrine abnormalities were defined by each hormone replacement therapy, including levothyroxine, hydrocortisone, and insulin, in which it is difficult to distinguish central or primary hormone defect. Also, only patients with hypothyroidism after thyroiditis were included. Type 1 diabetes was additionally defined by the name of the disease and strict self-injection fees. Regression analyses were performed to identify risk factors for endocrine abnormalities and the effect of endocrine abnormalities on OS, adjusting for confounders including the number and duration of ICI administrations.</p><p><strong>Results: </strong>Single and multiple endocrine abnormalities were observed in 12.0% and 1.4% of patients, respectively. The most common combination was hypothyroidism and adrenal insufficiency (1.3%). Kaplan-Meier analysis indicated better survival in patients with multiple and single endocrine abnormalities than in those without (P < .01). Multivariable analysis revealed lower mortality in patients with multiple and single endocrine abnormalities (adjusted hazard ratio [aHR] 0.39; 95% confidence interval [CI], 0.28-0.54, P < .01; aHR 0.65; 95% CI, 0.5-80.72, P < .01, respectively) than in those without. Mortality was significantly lower with multiple abnormalities than with single (aHR 0.56; 95% CI, 0.39-0.79, P < .01).</p><p><strong>Conclusions: </strong>The development of multiple endocrine abnormalities in patients treated with ICIs is associated with improved survival compared with that of patients with a single abnormality.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278144","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":"No More Free Lunch: Challenges to Mendelian Randomization Due to Sample Selection and Complex Methods.","authors":"Tianyuan Lu, Wenmin Zhang, Fergus W Hamilton, Guillaume Butler-Laporte, Nicholas J Timpson, George Davey Smith, J Brent Richards","doi":"10.1210/clinem/dgaf305","DOIUrl":"https://doi.org/10.1210/clinem/dgaf305","url":null,"abstract":"<p><p>Mendelian randomization (MR) is increasingly used in epidemiological studies to investigate causal relationships. MR depends on 3 fundamental instrumental variable assumptions: relevance, independence, and exclusion restriction. Studies often assume that MR mitigates bias from confounding due to the random allocation of genetic variants at conception. In this perspective, using causal directed acyclic graphs, we discuss several scenarios where biases in MR analyses may arise due to the nature of the data or methods being used. These include (1) collider bias due to the nonrandom selection of participants into study populations used for conducting genome-wide association studies (GWAS), (2) indirect genetic effects arising from population-based GWAS rather than within-family studies, and (3) collider bias due to gene-environment interaction effects on the exposure in nonlinear MR analyses. We provide practical considerations for examining and reducing these biases in MR analyses.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288155","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":"Levothyroxine in Pregnancy: Protective Neurodevelopmental Role Beyond Cognitive Outcomes?","authors":"Freddy J K Toloza, Sangeetha Gummalla, Spyridoula Maraka","doi":"10.1210/clinem/dgaf351","DOIUrl":"https://doi.org/10.1210/clinem/dgaf351","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278142","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":"Weight Trajectory Impacts Risk for Ten Distinct Cardiometabolic Diseases.","authors":"Alison Z Swartz, Kathryn Wood, Eric Farber-Eger, Alexander Petty, Heidi J Silver","doi":"10.1210/clinem/dgaf348","DOIUrl":"https://doi.org/10.1210/clinem/dgaf348","url":null,"abstract":"<p><strong>Context: </strong>Repetitive bouts of weight loss and regain, termed weight cycling, may exaggerate risk for cardiometabolic disease. We previously identified that weight cyclers were likely to have prescribed medications for hypertension, dyslipidemia, and diabetes - suggesting high prevalence of cardiometabolic disease.</p><p><strong>Objective: </strong>No prior study has compared relationships between longitudinal weight trajectory (weight stable, weight gainer, weight loser, or weight cycler) and commonly occurring specific cardiometabolic diseases among persons with similar high baseline BMI.</p><p><strong>Methods: </strong>Using de-identified electronic health record data from all adults treated at Vanderbilt University Medical Center between 1997 to 2020 and a landmark approach, we developed multivariate cox proportional hazards regression models to determine relationships between weight trajectory and risk for ten highly prevalent cardiometabolic diseases.</p><p><strong>Results: </strong>Compared to weight stability, weight cycling associated with almost 30% increased risk for obstructive sleep apnea (HR 1.28; 95% CI 1.15-1.42), MASLD (HR 1.28; 95% CI 1.08-1.51), and T2DM (HR 1.23; 95% CI 1.10-1.38). Weight cycling also associated with more than 50% increased risk for heart failure (HR 1.54; 95% CI 1.31-1.82), although both weight gain and weight loss also showed increased risk for HF (HR 1.29; 95% CI 1.08-1.55 and HR 1.32; 95% CI 1.10-1.58, respectively).</p><p><strong>Conclusions: </strong>The relationship between weight cycling and cardiometabolic disease risk was independent of having high baseline BMI, which was similar among weight trajectory groups. The present findings support promoting either weight stability at high BMI or weight loss if able to be maintained to prevent the incidence of a variety of cardiometabolic diseases.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278113","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":"Prediabetes subgroups, type 2 diabetes risk, and differential effects of preventive interventions.","authors":"Jeanette M Stafford, Ramon Casanova, Byron C Jaeger, Yitbarek Demesie, Brian J Wells, Michael P Bancks","doi":"10.1210/clinem/dgaf350","DOIUrl":"https://doi.org/10.1210/clinem/dgaf350","url":null,"abstract":"<p><strong>Objective: </strong>Prior studies have subclassified type 2 diabetes using statistical clustering approaches with clinical data, but few have subclassified prediabetes and assessed effects of preventive interventions. Our objective was to derive prediabetes subgroups based on clinical biomarkers and assess risk for incident diabetes and differential preventive intervention effects within the derived subgroups, with comparison to more simple modeling approaches.</p><p><strong>Methods: </strong>Baseline data for 3145 participants in the Diabetes Prevention Program trial were used to derive prediabetes subgroups using K-means clustering with data for 22 clinical biomarkers (sex-standardized). Cox proportional hazards regression was used to estimate hazard ratios (HR) for diabetes and differential intervention effects (intensive lifestyle, metformin, or placebo) by prediabetes subgroups and to compare the clustering strategy to a model with clinical variables.</p><p><strong>Results: </strong>We identified two prediabetes subgroups characterized by severe insulin resistance with severe obesity (subgroup 1, 31% of sample) and moderate insulin resistance with overweight or obesity (subgroup 2, 69%). Subgroup 1 had 58% higher risk for diabetes (HR: 1.58, 95% confidence interval: 1.31, 1.91) compared to subgroup 2. Randomization to lifestyle (compared to placebo) halved diabetes risk for both subgroups, while metformin provided greater benefit to subgroup 1 versus subgroup 2 (p for interaction <0.05). A clinical variable model discriminated diabetes risk better than the clustering strategy.</p><p><strong>Conclusion: </strong>Pathophysiologically distinct prediabetes subgroups differ in risk for diabetes and preventive benefit from metformin. These results support distinct mechanisms of diabetes susceptibility, however use of clinical prediction models to guide treatment decisions may provide adequate risk profiling.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268457","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 relationships between MASLD, extrahepatic multimorbidity and all-cause mortality in UK Biobank cohort.","authors":"Qi Feng, Chioma N Izzi-Engbeaya, Andrea D Branch, Benjamin H Mullish, Pinelopi Manousou, Mark Woodward","doi":"10.1210/clinem/dgaf342","DOIUrl":"https://doi.org/10.1210/clinem/dgaf342","url":null,"abstract":"<p><strong>Background & aims: </strong>This study aimed to estimate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), with and without multimorbidity, on all-cause mortality.</p><p><strong>Methods: </strong>We analysed data from the UK Biobank. MASLD was identified as a fatty liver index (FLI) ≥ 60 and presence of cardiometabolic risk factors. Multimorbidity was defined as ≥2 of the long-term conditions (LTCs) in a pre-specified list of 47 extrahepatic conditions. Hazard ratios (HRs) from adjusted Cox models quantified the association between MASLD, multimorbidity and all-cause mortality.</p><p><strong>Results: </strong>Of the 438,840 participants, 131,020 (29.9%) had MASLD at baseline. The participants with MASLD at baseline had a higher prevalence of multimorbidity than those without (21.3% vs. 14.4%). In addition to cardiometabolic risk factors, MASLD was strongly associated with several LTCs, particularly metabolic, cardiovascular, cancers, kidney, mental/behavioural, and respiratory diseases. During a median follow-up of 13 years, MASLD was associated with higher mortality (HR 1.16 (95%CI: 1.13, 1.19)), with stronger associations in females and in those with low LTC counts (≤3 LTCs). Each additional LTC at baseline was associated with 30% and 38% higher mortality in MASLD (HR 1.30 (1.29, 1.32)) and non-MASLD (HR 1.38 (1.37, 1.40)) populations, respectively. Among the 47 LTCs, 16 were associated with increased mortality in people with MASLD.</p><p><strong>Conclusion: </strong>Those with MASLD exhibited a higher prevalence of extrahepatic multimorbidity and a 16% higher rate of mortality than those without, underscoring the impact of liver steatosis on mortality and highlighting the need to target LTCs to improve outcomes and reduce healthcare burdens.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268483","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":"Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.","authors":"Yahao Wang, Yue Zhou, Zhihong Wang, Yunzhi Ni, Gerald J Prud'homme, Qinghua Wang","doi":"10.1210/clinem/dgaf336","DOIUrl":"https://doi.org/10.1210/clinem/dgaf336","url":null,"abstract":"<p><strong>Objective: </strong>New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.</p><p><strong>Methods: </strong>We searched PubMed, Embase and Cochrane Library database to identify randomized controlled trials (RCTs) that compared GLP-1RAs with placebo or active agents with respect to the efficacy in patients with MASLD/MASH. The effects of GLP-1RAs on liver fat content (LFC) by imaging, liver histology, serum liver enzymes, and noninvasive fibrosis indexes (fibrosis-4, NFS, CK-18, procollagen III and liver stiffness) were evaluated. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model.</p><p><strong>Results: </strong>25 RCTs involving 2600 patients that used GLP-1RAs including liraglutide, exenatide, dulaglutide, semaglutide, tirzepatide, efinopegdutide, survodutide and retatrutide were included. Overall, GLP-1RAs treatment for a median of 24 weeks demonstrated a significant reduction in LFC by 5.21%, with the retatrutide displaying the most obvious treatment effects. GLP-1RAs treatment induced significant histological improvements in steatosis, hepatocellular ballooning and lobular inflammation, but non-significantly improved fibrosis, with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. GLP-1RAs treatment significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) compared with control. GLP-1RAs also significantly improved liver stiffness, with semaglutide displaying the most obvious treatment effect. No drug-related adverse effects involving the liver was observed.</p><p><strong>Conclusion: </strong>GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning and lobular inflammation, without worsening of fibrosis in MASLD and MASH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259944","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}