Search Results (2,295)

Background/Objectives: The cardiometabolic consequences of sarcopenic obesity (SO) remain poorly characterized in Latin America. We hypothesized that SO uniquely concentrates aortic stiffness, metabolic syndrome, and vitamin D deficiency in older Mexican adults, and that handgrip strength exhibits a dose–response relationship with cardiometabolic risk independent of adiposity. Methods: We conducted a cross-sectional analysis of 2087 adults ≥ 50 years from the Mexican Health and Aging Study (MHAS) 2012. Four phenotypes were defined using EWGSOP2 criteria: lean–fit, lean–sarcopenic, obese–non-sarcopenic, and obese–sarcopenic (BMI ≥ 30 kg/m²). Outcomes were pulse pressure (PP, aortic stiffness proxy), metabolic syndrome (modified IDF criteria), and serum 25(OH)D. Normality tests confirmed non-normal distribution (p < 0.001). Given heteroscedasticity (Breusch–Pagan p < 0.001), HC3 robust standard errors were used. Regression models were sex-adjusted and sex-stratified. Results: The sample showed high cardiometabolic burden: mean HbA1c 6.91% (35.3% ≥ 6.5%); metabolic syndrome 57.6%; mean PP 60.7 ± 17.9 mmHg; mean gait speed 0.708 m/s (70.4% slow). Phenotype distribution: lean–fit 12.3%; lean–sarcopenic 47.3%; obese–non-sarcopenic 8.7%; obese–sarcopenic 31.7%. In multivariable models, handgrip strength was an independent protective predictor of PP (beta = −0.09 per kg; 95% CI: −0.17 to −0.01; p = 0.033), with a sex-specific effect in women (beta = −0.13; p = 0.010). Conclusions: SO is highly prevalent in older Mexican adults and associates with an adverse cardiometabolic profile. Handgrip strength shows a protective dose–response association with cardiometabolic risk independent of adiposity, identifying muscle function as a candidate modifiable factor that warrants confirmation in longitudinal and interventional studies. The obese–non-sarcopenic phenotype exhibited the lowest PP, unveiling the sarcopenic obesity paradox: adiposity without muscle function loss does not promote arterial stiffening. Full article

Pediatric sleep-disordered breathing (SDB) is underdiagnosed despite its associations with adverse neurobehavioral, psychosocial, and cardiometabolic outcomes. Pediatric dental providers routinely evaluate craniofacial growth and maintain longitudinal contact with children, yet practical approaches for integrating SDB risk assessment into dental settings remain limited. This protocol describes a prospective, cross-sectional observational study that will enroll 60 school-aged children aged 8–13 years from a university-based pediatric dental clinic and classify them as low-risk or high-risk for SDB using the Pediatric Sleep Questionnaire (PSQ; threshold ≥ 0.33). The primary aim is to examine associations between PSQ-based risk classification and objective physiologic sleep parameters, including the Apnea–Hypopnea Index, Respiratory Disturbance Index, Sleep Apnea Indicator, and Sleep Quality Index, obtained from a U.S. Food and Drug Administration-cleared wearable home sleep monitor—SleepImage Ring (MyCardio LLC, Denver, CO, USA)—worn for a minimum of three consecutive nights. Secondary aims will evaluate associations between SDB risk classification and body mass index, Mallampati score, Brodsky tonsillar grade, and psychosocial functioning (anxiety, depression, perceived stress, and daytime sleepiness). Exploratory craniofacial analyses will be conducted among participants with clinically available lateral cephalometric radiographs. This protocol could position pediatric dental visits as an accessible touchpoint for early identification of children with unrecognized SDB and inform pathways for timely referral. Protocol Version: 1.4, dated 13 May 2026. Trial Registration: ClinicalTrials.gov NCT07581938. Full article

Background/Objectives: Incretin-based pharmacotherapies are the most effective non-surgical treatments for obesity to date, yet 85% of patients discontinue within the second year of real-world use. No established framework exists for managing this post-cessation transition. This narrative review evaluates the evidence for structured exercise to mitigate physiological rebound and support long-term weight management following discontinuation. Methods: A narrative review was conducted per Assessment of Narrative Review Articles (SANRA) guidelines using PubMed, Scopus, and Web of Science from January 2005 through to June 2026. Results: Post-cessation weight regain averages 5.6 kg within one year and is observationally associated with dose-dependent cardiometabolic worsening. Lean mass losses averaging 6–7 kg and reductions in bone mineral density are seen during active treatment, creating a metabolically unfavorable state at cessation compounded by fat-preferential regain. Exercise and pharmacotherapy generate fundamentally different body composition outcomes. Exercise preserves lean mass, bone density, cardiorespiratory fitness, and insulin sensitivity, while pharmacotherapy alone does not, with downstream implications for resting metabolic rate and post-cessation rebound. Controlled trial data show exercise initiated during incretin treatment is associated with significantly less weight regain, greater sustained weight loss, and maintained physical activity levels one year after medication and supervised program end. This evidence derives from a single liraglutide-based trial and may not generalize directly to semaglutide, tirzepatide, or next-generation agents. Real-world data associate exercise counseling with durable weight loss after discontinuation. Conclusions: No randomized controlled trial has directly evaluated exercise at pharmacotherapy cessation; conclusions are based on post-treatment extension, real-world observational, and mechanistic evidence. Combined aerobic and resistance training is a biologically plausible, low-risk adjunct to incretin-based pharmacotherapies. Resistance training, adequate dietary protein, and individualized clinical screening are likely important components pending direct evidence from post-cessation trials. Full article

Objective: Hepatic steatosis commonly coexists with cardiometabolic risk factors, yet circadian blood pressure patterns in adults with hepatic steatosis remain incompletely characterized. This study aimed to describe ambulatory blood pressure patterns in adults with ultrasonographically detected moderate-to-severe hepatic steatosis. Methods: This single-center prospective observational study enrolled adults with grade 2 or 3 hepatic steatosis on abdominal ultrasonography between August 2023 and August 2024. All participants underwent 24-h ambulatory blood pressure monitoring after enrollment. Patients were classified as dipper or non-dipper according to nocturnal blood pressure decline, and clinical, biochemical, ultrasonographic, and ambulatory parameters were compared. Results: Among 137 patients, 43 (31.4%) had a dipper pattern and 94 (68.6%) had a non-dipper pattern. Grade 2 and grade 3 steatosis were present in 125 (91.2%) and 12 (8.8%) patients, respectively. In the exploratory multivariable analysis, age, sex, antihypertensive treatment, and ultrasonographic steatosis grade were not independently associated with non-dipping status. Ambulatory hypertension thresholds were met more often in the non-dipper group [72 (76.6%) vs. 25 (58.1%), p = 0.027]. Nocturnal hypertension was more frequent in the non-dipper group [72 (76.6%) vs. 22 (51.2%), p = 0.003]. The non-dipper group had higher 24-h systolic blood pressure [134.0 (122.0–145.0) vs. 130.0 (118.5–136.0) mmHg, p = 0.027]. The median nocturnal systolic blood pressure decline in the overall cohort was 6.0% [2.6–11.3], whereas daytime systolic and diastolic blood pressure values were comparable between groups. Conclusions: Non-dipping blood pressure was frequent in adults with moderate-to-severe hepatic steatosis. Ambulatory blood pressure monitoring provides a descriptive assessment of nocturnal blood pressure patterns in this selected hepatic steatosis cohort. Full article

Background: Contemporary antidiabetic therapy has evolved from a glucose-centered approach toward integrated cardiometabolic risk reduction. However, real-world evidence regarding treatment patterns and their association with glycemic and cardiovascular–renal profiles remain limited. Methods: This retrospective observational study included 250 adults with type 2 diabetes mellitus receiving non-insulin glucose-lowering therapy in routine specialist clinical practice. Demographic, clinical, biochemical, and pharmacological data were extracted from medical records. Glycemic control was assessed using HbA1c levels and HbA1c variation, while cardiovascular–renal parameters included estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), lipid profile, blood pressure, and heart failure prevalence. Comparative analyses and multivariate logistic regression were performed. Results: The cohort had a mean age of 61.8 ± 11.3 years, and all patients had type 2 diabetes mellitus (100.0%). Obesity, metabolic syndrome, hypertension, ischemic heart disease, and chronic kidney disease were highly prevalent. Metformin was the most frequently prescribed therapy (58.8%), followed by GLP-1 receptor agonists (28.8%) and SGLT-2 inhibitors (27.6%). Patients receiving GLP-1 receptor agonists or SGLT-2 inhibitors showed numerically lower HbA1c values and greater HbA1c reductions compared with conventional therapies. However, differences in HbA1c, CRP, and eGFR were not statistically significant after correction for multiple comparisons. Longer diabetes duration independently predicted poor glycemic control, whereas increasing age was associated with a lower probability of HbA1c > 7%. Conclusions: Contemporary antidiabetic therapies were associated with favorable numerical cardiometabolic trends, although these associations did not remain statistically significant after multiple-comparison correction. The findings should therefore be considered exploratory and hypothesis-generating. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) and arterial hypertension (AH) frequently coexist and are major risk factors for cardiovascular disease (CVD) and chronic kidney disease. Although the Mediterranean diet (MeDi) is widely recommended in cardiometabolic management, longitudinal real-world evidence regarding dietary adherence, body composition, and the role of continuous dietitian-led follow-up remains limited. Methods: This three-year prospective observational study included 158 adults with T2DM and AH treated at the Outpatient Clinic for Clinical Nutrition, University Hospital Centre Split, Croatia. Body composition was assessed using multi-frequency bioelectrical impedance analysis, dietary adherence using the Mediterranean Diet Serving Score (MDSS), and renal and metabolic parameters using standard laboratory methods. Participants were stratified according to attendance at scheduled dietitian-led follow-up visits. Results: Significant reductions were observed in body weight, body mass index (BMI), waist circumference, muscle mass, skeletal muscle index, and phase angle (PhA) during follow-up (all p < 0.001). Lipid profile improved, with reductions in total cholesterol and low-density lipoprotein levels and an increase in high-density lipoprotein concentrations. In contrast, renal function declined, as evidenced by increased creatinine and urea levels and decreased estimated glomerular filtration rate (eGFR). CVD incidence increased significantly during follow-up (p < 0.001). Although overall adherence to the MeDi improved, only 17.8% of participants achieved high adherence. Participants attending regular dietitian-led follow-up demonstrated significantly higher MDSS scores, greater adherence to the MeDi, and higher phase angle values compared with participants without regular follow-up. Conclusions: Adults with T2DM and AH demonstrated partial enhancement of MeDi adherence over three years; although the lipid profile also improved, this could not be attributed to diet and may largely reflect pharmacological treatment. These changes were accompanied by progressive muscle mass loss, declining renal function, and increased cardiovascular burden. Continuous dietitian-led follow-up was associated with superior dietary quality and better nutritional status, supporting the importance of individualized, multidisciplinary approaches integrating sustained nutritional counselling, lean mass preservation, and structured physical activity in long-term cardiometabolic care. Full article

Background/Objectives: Metabolic indices such as HOMA-IR, METS-IR and TyG play a critical role in determining cardiometabolic risk and insulin resistance in clinical practice. This study aims to simultaneously predict these three indices using ensemble learning models, based on demographic, clinical, and laboratory data from patients with gout. Methods: Demographic, retrospective clinical, and laboratory data from 411 patients diagnosed with gout were analyzed, and a logarithmic transformation was applied to address skewness in the target variable. A genetic algorithm was used to identify relevant features for predicting metabolic indices, and four scenarios were designed. Five ensemble learning models were optimized using fine-tuning with Optuna. The models’ decisions were clinically validated using SHAP analysis. Results: Across all scenarios, the CatBoost model combined with the GA + Log-Transformed framework achieved the highest prediction accuracy and the lowest error rates. Notably, when predicting the TyG index, it simulated the underlying formula with near-perfect accuracy. SHAP analysis confirmed that CatBoost successfully mapped clinical pathophysiology by prioritizing insulin levels for HOMA-IR, BMI for METS-IR, and triglyceride variance for the TyG index. Conclusions: The proposed GA + Log-Transformed CatBoost workflow provides a highly accurate, non-invasive and interpretable clinical decision support system. This study demonstrates that the ensemble architecture effectively captures complex pathophysiological patterns aligned with medical knowledge rather than merely memorizing statistical noise. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognised as a systemic disorder with clinically relevant extrahepatic manifestations. Pancreatic diseases have gained particular attention in this context, as they share key metabolic and inflammatory mechanisms with MASLD and may influence each other’s natural history and clinical outcomes. Beyond shared cardiometabolic risk factors, emerging evidence suggests that MASLD may actively contribute to pancreatic dysfunction and disease progression, supporting a bidirectional liver–pancreas relationship. Recognition of this association is essential to improve risk stratification, diagnostic assessment, and clinical management. This review summarises the current evidence linking MASLD with pancreatic disorders, focusing on acute and chronic pancreatitis, pancreatic cancer, and fatty pancreas. We examine shared pathophysiological pathways and discuss how these interactions may affect disease progression, nutritional status, diagnostic strategies, and therapeutic decision-making. We also address key clinical challenges, including alcohol assessment and MASLD–MetALD misclassification, highlight current knowledge gaps, and provide scenario-specific recommendations. Full article

Metabolomic aging clocks—quantitative models that estimate biological age based on small-molecule profiles in biological fluids—have become dynamic tools for assessing individual aging trajectories and predicting the risk of age-related diseases. Although NMR-based approaches have been previously reviewed, the analytical landscape of mass spectrometry (MS)-based metabolomic clocks has not been systematically assessed. This review examines the key components of the MS-based analytical workflow underlying the development of metabolomic aging clocks, including biological matrix selection, chromatographic separation strategies, MS instrumentation, data preprocessing, metabolite annotation, and machine learning-based modeling approaches. Twelve published studies on MS-based metabolomic clocks were identified and systematically compared. These clocks provide predictions of chronological age with mean absolute errors of 3.5–10 years and demonstrate robust associations between metabolomic age acceleration and cardiometabolic risk, frailty, and mortality. Recurrent age-related metabolite classes include tryptophan–kynurenine pathway metabolites, acylcarnitines, sphingolipids, modified nucleosides, and tricarboxylic acid (TCA) cycle intermediates. Currently, liquid chromatography with electrospray ionization (LC-ESI) coupled to high-resolution QTOF or Orbitrap instruments dominates current workflows, with elastic net regression being the most commonly applied modeling strategy. Significant heterogeneity in analytical conditions, incomplete methodological descriptions, and limited cross-study validation remain key obstacles to clinical application. Standardization of pre-analytical protocols, the use of certified reference materials, and harmonized validation frameworks are identified as critical priorities for advancing mass spectrometry-based metabolomic clocks toward clinical translation. Full article

Background: Visceral obesity is increasingly recognised not as a simple excess of adipose tissue, but as a systemic pathological condition characterised by profound metabolic, endocrine, and immune dysregulation. Visceral adipose tissue (VAT) operates as an autonomous neuro-immune-endocrine organ whose dysfunctional expansion drives insulin resistance, atherogenesis, and accelerated cellular ageing through mechanisms converging on chronic low-grade sterile inflammation, referred to as inflammaging. Objectives: This narrative review integrates evidence across four domains: (1) the multi-system clinical complications of visceral obesity and the methodological controversies surrounding its measurement; (2) the cellular heterogeneity, immunometabolic reprogramming, and molecular mechanisms through which excess VAT accelerates biological ageing, with a focus on genomic instability, mitochondrial dysfunction, the NAD⁺/sirtuin regulatory axis, cellular senescence, and inter-organ communication; (3) the role of bioelectrical impedance analysis (BIA)—particularly phase angle—as a non-invasive functional biomarker of biological age and longevity, positioned critically against alternative assessment methods; and (4) current knowledge gaps and priorities for future research. Methods: A narrative review of PubMed/MEDLINE, Google Scholar, and the Cochrane Library was conducted using MeSH terms and free-text keywords including visceral obesity, bioelectrical impedance analysis, phase angle, sarcopenia, inflammaging, mitochondrial dysfunction, cellular senescence, epigenetic clocks, NAD⁺, sirtuin, and longevity, supplemented by citation-tracking of retrieved reviews. English-language articles published up to April 2025 were considered, prioritising systematic reviews, meta-analyses, and prospective cohort studies; formal risk-of-bias tools and quantitative synthesis were not applied, consistent with a narrative review design. Results and Discussion: BIA-derived phase angle constitutes a macroscopic electrobiological correlate of inflammaging: low phase angle values in visceral obese subjects overlap with those of frail elderly individuals, reflecting impaired membrane integrity, loss of active cell mass, and altered ICW/ECW balance. However, this evidence base remains largely cross-sectional and correlative; the directionality and population-specific calibration of BIA-derived indices constitute the principal unresolved methodological questions. Integration with epigenetic clocks, circulating NAD⁺ levels, and gut microbiome indices offers a framework for dynamic biological age assessment, though prospective interventional validation is still lacking. Sarcopenic obesity, evaluated through EWGSOP2 combined with BIA-derived skeletal muscle mass index and handgrip dynamometry, represents a critical comorbidity demanding integrated therapeutic targeting. Conclusions: BIA provides a quantitative, accessible correlate for translating cellular metabolic health into clinically actionable parameters, complementary to rather than a replacement for anthropometric and imaging-based methods. Optimising phase angle and reducing VAT through anti-inflammatory nutrition, exercise, and nutraceutical strategies targeting the NAD⁺/sirtuin and mTOR/AMPK axes constitutes a measurable objective for the promotion of healthy longevity, contingent on the longitudinal, mechanistic studies identified as priorities in this review. Full article

Background and Objectives: Chronotype and sleep quality are related but non-identical dimensions of sleep health. We examined whether later chronotype is associated with subclinical visceral adiposity and atherogenic dyslipidaemia independently of perceived sleep quality, and whether this association differs by sex, in adults without previously diagnosed chronic disease. Materials and Methods: This single-centre cross-sectional study included 282 adults without previously diagnosed chronic disease or regular medication use. Chronotype was assessed with the Morningness–Eveningness Questionnaire (MEQ) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Composite cardiometabolic indices were calculated from routine anthropometric and biochemical data. Primary dependent variables were log-transformed Visceral Adiposity Index (log[VAI]) and Atherogenic Index of Plasma (AIP). Multivariable linear models used heteroscedasticity-consistent type 3 (HC3) robust standard errors and adjusted for age, sex, education, physical activity, and PSQI; body mass index (BMI) was additionally included in the AIP model. Sex × MEQ interactions, false-discovery-rate (FDR) correction, and glycaemic sensitivity analyses were performed. Results: Median age was 28.0 years; 50.4% were women, 25.9% were evening type, and 51.8% had poor sleep quality. Higher MEQ score (greater morningness) was independently associated with lower log(VAI) (B = −0.0096; 95% confidence interval (CI), −0.0159 to −0.0033; β = −0.190; p = 0.003) and AIP (B = −0.0035; 95% CI, −0.0063 to −0.0008; β = −0.160; p = 0.011), whereas PSQI was not independently associated with either outcome. Sex × MEQ interactions were nominally significant and estimates were stronger in women, but interaction terms did not survive FDR correction. Associations persisted after excluding diabetes-range glycaemia but attenuated in strictly normoglycaemic participants. Conclusions: Later chronotype was associated with a less favourable subclinical adiposity–atherogenic profile independently of perceived sleep quality. Findings are cross-sectional, and the sex-specific pattern is hypothesis-generating. Prospective studies with objective circadian, sleep, dietary-timing, behavioural, and hormonal measures are required. Full article

Aim: To identify the relationship between joint sleep patterns and the incidence of cardiometabolic diseases (CMDs) and multimorbidity (CMM) as well as the mediating effects of plasma metabolites. Methods: This prospective study included 190,827 participants from the UK Biobank. The joint sleep pattern was evaluated by the healthy sleep score according to five sleep factors (chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness). Cox proportional hazards models were utilized to evaluate the relationship between sleep-related metabolites and the incidence of CMM and CMDs. Mediation analyses were conducted to quantify the potential mediating effects of circulating metabolites. Results: After a median follow-up of 13.5 years, 24,602 incident cases of CMDs and 2740 incident cases of CMM were identified. Per 1-decrement of sleep score was associated with 10.5% and 15.1% increased risks of CMDs and CMM, respectively. However, sleep was not associated with the progression from the first disease to CMM. A total of 152 metabolites were identified to be associated with sleep patterns, among which lipoproteins emerged as the predominant class. Most of the metabolites showed mediation effects on the association between sleep and outcomes. Conclusions: Poor sleep pattern was associated with increased risk of CMDs and CMM. Differences in metabolites, especially lipoproteins, might partially explain the association between sleep pattern and cardiometabolic health. Full article

Background: Childhood obesity is a growing health concern and added sugar intake has been associated with increased obesity risk. Emerging evidence suggests that miR-143-5p and miR-223-3p are involved in metabolic regulation. Therefore, this study evaluated their plasma expression according to added sugar intake and their association with cardiometabolic risk parameters. Methods: This cross-sectional study included 91 children aged 6–12 years, comprising 44 with normal weight and 47 with overweight/obesity. Anthropometric measurements, clinical characteristics, and dietary added sugar intake were assessed. Plasma expression of miR-143-5p and miR-223-3p was quantified by RT-qPCR. Results: Compared with low added sugar intake, high added sugar intake was associated with lower plasma miR-143-5p expression and higher miR-223-3p expression. Both miR-143-5p and miR-223-3p expression levels were higher in children with overweight/obesity and insulin resistance than in their respective counterparts. In adjusted analyses, neither miRNA was associated with cardiometabolic risk parameters. However, added sugar intake was positively associated with miR-223-3p expression (β = 0.188, 95% CI: 0.022, 0.354) and glucose levels (β = 1.944, 95% CI: 0.133, 3.755). Conclusions: These findings suggest that higher added sugar intake is associated with altered circulating miRNA expression and higher fasting glucose concentrations in school-aged children. Full article

Despite the success of modern antiretroviral therapy in achieving virological suppression, people living with HIV face an elevated risk of cardiovascular diseases, particularly heart failure with preserved ejection fraction. This study evaluates the cardiometabolic phenotype and functional capacity in a Romanian HIV cohort to delineate the metabolic footprint of chronic infection. In this cross-sectional study based on prospectively collected, protocol-driven phenotyping, we evaluated 50 consecutive outpatients from a university-affiliated infectious diseases clinic in Timisoara. Eligibility strictly required clinical stability and sustained virological suppression (plasma HIV-RNA < 50 copies/mL for ≥12 months). The analysis revealed widespread metabolic dysregulation, with 52% exhibiting excess weight and 64% showing atherogenic dyslipidemia. Integrase strand transfer inhibitor-based regimens were significantly correlated with an increased body mass index (p = 0.034) and elevated LDL cholesterol (aOR = 2.4, 95% CI [1.18–4.95], p = 0.022). Furthermore, we observed a pronounced metabolic age gap (+4.5 ± 2.8 years), defined as the deviation of bioimpedance-estimated metabolic age from the patients’ chronological age. This gap (p = 0.028), alongside historical immunodeficiency indicated by a low nadir CD4+ count (aOR = 0.998, 95% CI [0.991–0.999], p = 0.021), strongly predicted exercise intolerance, independent of current immune reconstruction. Sarcopenic obesity (present in 18% of the cohort) and an elevated triglycerides-to-HDL ratio (aOR = 2.14, 95% CI [1.15–3.98], p = 0.016) emerged as robust independent negative predictors of functional capacity. Additionally, subclinical myocardial remodeling, evidenced by impaired Global Longitudinal Strain, significantly predicted reduced aerobic capacity (aOR = 0.72, 95% CI [0.58–0.89], p = 0.003). Consequently, contemporary HIV management must transition beyond virological control to integrated cardiometabolic screening. Utilizing cardiopulmonary exercise testing, echocardiography, and metabolic biomarkers is critical for the early identification of subclinical “functional HIV-associated frailty” and mitigating the trajectory toward overt cardiovascular diseases. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and related incretin-based therapies are highly effective anti-obesity treatments, but weight loss may also include reductions in fat-free mass, raising concern for selected patients at risk of sarcopenia. This narrative review summarizes current evidence and practical, evidence-informed strategies to support muscle health during GLP-1 RA-based anti-obesity therapy. Particular emphasis is placed on identifying higher-risk patients, including older adults, frail individuals, patients with low baseline muscle mass or strength, sarcopenic obesity, chronic kidney disease, low physical activity, or rapid weight loss. Preventive strategies include baseline assessment of body composition and muscle function, individualized resistance and multicomponent exercise, adequate protein intake, attention to nutritional adequacy, and periodic monitoring of body composition, strength, and physical performance. Treatment pace and dose escalation may also be individualized in higher-risk patients when unfavorable changes in fat-free mass or function occur. Current evidence remains limited, and many recommendations are extrapolated from weight-loss, nutrition, exercise, and sarcopenia literature rather than GLP-1 RA-specific trials. Overall, a risk-stratified and multidisciplinary approach may help preserve muscle mass and function while maintaining the cardiometabolic benefits of GLP-1 RA-based therapy. Full article