Search Results (461)

Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes and obesity treatment and may influence reward-related behaviors, including alcohol use. This study aimed to evaluate the effects of GLP-1RAs on alcohol consumption and related outcomes in adults with alcohol use or alcohol use disorder (AUD). Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed and Web of Science were searched from inception to December 2025. Eligible studies included randomized controlled trials (RCTs), secondary analyses of RCTs, and observational studies reporting quantitative alcohol consumption outcomes. Data extraction and risk of bias assessment (RoB 2 and ROBINS-I) were performed independently by two reviewers. Results: Five studies (n = 49,892) were included, comprising three RCT-based analyses and one large cohort study. Semaglutide and dulaglutide were associated with modest reductions in alcohol consumption and craving in several studies, with statistically significant improvements in selected behavioral outcomes. In contrast, exenatide did not demonstrate significant effects in the overall AUD population, with signals limited to subgroups. The cohort study showed small but statistically significant reductions in AUDIT-C scores following GLP-1RA initiation. Objective measures (e.g., PEth, breath alcohol concentration) showed reductions in selected contexts but were reported in a few studies. Conclusions: GLP-1RAs may be associated with modest reductions in alcohol consumption, but evidence remains limited and heterogeneous. Larger, well-designed RCTs are needed to define their role in the management of AUD. Full article

Background: Thoracic aortic aneurysm (TAA) remains a high-risk vascular condition despite major advances in imaging surveillance, operative repair, and endovascular therapy. Medical management still relies largely on blood pressure control and global cardiovascular risk reduction. Renin–angiotensin–aldosterone system (RAAS) inhibitors are frequently used in TAA, but contemporary data evaluating survival and cardiovascular outcomes in broad TAA populations are limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) have established cardiometabolic benefits, yet their role in TAA has not been well defined. Methods: We performed a retrospective multicenter cohort study of adults with imaging-confirmed TAA diagnosed between 1 January 2018 and 1 January 2026 using a Mayo Clinic electronic data platform encompassing more than 15 million patient records. Primary exposures were documented use of RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors, evaluated individually and in prespecified combination-therapy analyses. Propensity score matching was used to balance demographics, comorbidities, aortic procedural history, and concomitant cardiovascular medications. Primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE) through 60 months. Results: The study included 162,126 patients with TAA. After matching, RAAS inhibitor use was associated with higher 60-month overall survival (88.3% vs. 85.5%; hazard ratio [HR], 0.79; 95% CI, 0.76–0.83; p < 0.001) and MACE-free survival (86.1% vs. 84.2%; HR, 0.87; 95% CI, 0.83–0.91; p < 0.001). GLP-1 RA therapy was associated with higher overall survival (97.5% vs. 92.5%; HR, 0.32; 95% CI, 0.27–0.38; p < 0.001) and MACE-free survival (93.2% vs. 89.3%; HR, 0.62; 95% CI, 0.56–0.70; p < 0.001). SGLT2 inhibitor therapy was similarly associated with higher overall survival (89.8% vs. 81.5%; HR, 0.51; 95% CI, 0.47–0.54; p < 0.001) and MACE-free survival (86.3% vs. 79.1%; HR, 0.62; 95% CI, 0.58–0.66; p < 0.001). Combination therapy with RAAS inhibitors plus either GLP-1 RAs or SGLT2 inhibitors was associated with incremental improvements in overall survival and MACE-free survival compared with GLP-1 RA or SGLT2 inhibitor monotherapy. Conclusions: In this large propensity-matched TAA cohort, RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors were each associated with improved survival and fewer major cardiovascular events, with additional benefit observed for RAAS-based combination therapy. These findings support further prospective investigation of integrated cardiometabolic and vascular-targeted therapy in TAA, while underscoring that observational associations should not be interpreted as proof of aneurysm-specific disease modification. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide (LIR), are widely used in humans to treat type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease. In mammals, GLP-1 RAs have been shown to influence hepatic lipid metabolism, although the underlying mechanisms remain unclear. In fish, GLP-1 also plays an important role in regulating hepatic processes, including glycogenolysis, gluconeogenesis, and lipolysis. However, the effects of GLP-1 RAs on liver lipid metabolism in fish remain largely unexplored. Objective: This study aimed to evaluate the effects of LIR on lipid target genes using primary hepatocytes from brown trout as an in vitro model. Methodology: After 24 h, a hepatocyte monolayer culture was established, and cells were exposed for 24 and 48 h to supplemented L-15 medium (control), 0.1% dimethyl sulfoxide in supplemented L-15 medium (solvent control), and five single exposures to LIR at 1, 10, 100, 500, and 1000 nM. After 24 and 48 h, cell viability was assessed using the trypan blue exclusion assay. Gene expression was analysed by real-time qPCR, targeting genes involved in lipogenesis, lipid transport, and cholesterol efflux. Results: No concentration-dependent effects on cell viability were observed. Gene expression analysis showed that LIR exposure modulated the mRNA levels of lipid-related genes, including acetyl-CoA carboxylase (ACC), acyl-CoA long-chain synthetase 1 (Acsl1), and fatty acid synthase (FAS), with time being the main influencing factor. Overall, expression levels were higher at 48 h compared to 24 h. Additionally, dose-dependent effects were observed for ACC expression, with higher LIR concentrations showing significant differences compared to controls. Conclusions: These findings indicate that LIR modulates lipid-related gene expression in primary hepatocytes of brown trout without affecting cell viability. The results suggest that GLP-1 receptor activation may influence key pathways involved in hepatic lipid metabolism, with time-dependent effects playing a predominant role. Overall, this study supports the use of brown trout primary hepatocytes as a suitable in vitro model for investigating hepatic lipid responses to LIR and other GLP-1 receptor agonists, while providing initial insight into their potential effects in fish. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have demonstrated efficacy for weight loss in obesity; however, up to 40% of weight lost may derive from lean body mass. The ketogenic diet independently improves insulin sensitivity and promotes fat oxidation while preserving lean tissue. This study aimed to describe changes in body composition, insulin sensitivity, and cardiometabolic markers in patients who followed a personalized ketogenic dietary protocol while receiving low-dose semaglutide over a 6-month insulin resistance reversal program. Methods: Seven analyzed adults (six female, one male) with overweight or obesity (baseline BMI 25.6–47.2 kg/m²) participated in a clinician-supervised 6-month program combining a whole-food ketogenic diet with semaglutide (≤1.0 mg/week). Body composition and fasting metabolic markers were assessed at 1, 3, and 6 months. Results: Mean total weight loss was 21.9 kg, of which a mean of 92% was attributable to BIA-estimated fat mass. Skeletal muscle mass was largely preserved as measured by BIA (mean loss 1.2 kg), and one patient gained lean tissue. Fasting insulin declined by a mean of 15.6 µIU/mL. Visceral fat decreased by a mean of 37.0%. Six of seven patients showed reductions in high-sensitivity C-reactive protein. Triglycerides decreased in six of seven patients, and HDL cholesterol increased in all seven. LDL cholesterol responses were heterogeneous. Conclusions: In this small, uncontrolled case series, combining a ketogenic diet with low-dose semaglutide was associated with substantial fat loss, apparent preservation of lean mass as measured by BIA, and improvements in insulin sensitivity and cardiometabolic markers. Because the semaglutide dose and dietary protocol were individualized to each patient’s response, the program illustrates a personalized approach to insulin resistance. These preliminary findings are hypothesis-generating and warrant confirmation in controlled prospective studies. Full article

GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes and obesity and are increasingly relevant in periodontal and implant practice. This review covers mechanisms, preclinical and early human evidence, and practical periodontal considerations; the structured database search is conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) and the International Committee of Medical Journal Editors (ICMJE) principles. Two pathways explain GLP-1RAs’ relevance: indirect effects from better glycemic control, weight loss, and reduced inflammation; and direct tissue effects involving GLP-1R signaling and the GLP-1/dipeptidyl peptidase-4 (DPP-4) axis. Preclinical studies show reduced inflammation, osteoclast activity, and alveolar bone loss, along with improved periodontal stem cell function under hyperglycemia or inflammation via Nuclear Factor-kappaB (NF-kappaB), Wingless-related integration site (Wnt)/beta-catenin, and Mitogen-Activated Protein Kinase (MAPK) pathways. Animal studies on implants and local delivery, including exendin-4 platforms, suggest osteometabolic benefits. Human data are limited and mostly observational, and confounders include metabolic status, smoking, medication, and nutrition. Oral side effects such as xerostomia and dehydration are also noted. At present, GLP-1RA therapy should be regarded as a contextual modifier of periodontal risk and healing capacity rather than as a stand-alone periodontal therapy. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to have beneficial effects in T2D, reducing hepatic lipid storage and improving metabolic dysfunction-associated steatotic liver disease. However, sex and reproductive age may influence their effect. We investigated the effect of liraglutide administration (0.2 mg/kg/day subcutaneously for 8 weeks) on metabolic disorders in relation to sex and reproductive age, using male, female and ovariectomized female hereditary hypertriglyceridemic (HHTg) rats as a prediabetic model. Liraglutide improved glucose tolerance in all HHTg rats. Female and ovariectomized (OVX) female rats showed a stronger effect of lipid metabolism and visceral adiposity than males. Moreover, no changes in hepatic triacylglycerol (TAG) accumulation were observed in males. Liraglutide partially reversed ovariectomy effects, such as increased body weight, visceral obesity and impaired glucose tolerance. Compared with males, female and OVX female rats showed more significant changes in hepatic gene expression involved in lipogenesis (Scd-1, Srebp1, Pparγ), fatty acid and lipid metabolism (Pparα, Hmgcr, Srebp2) and fibrosis (Tgfβ), which may improve hepatic lipid metabolism. Females of fertile age showed greater improvements in insulin sensitivity, reductions in ectopic lipid accumulation, and improvements in lipid metabolism. Depending on sex and reproductive status, liraglutide can mitigate fatty liver before diabetes onset. Full article

Objective: Insulin resistance is a key pathophysiological driver linking obesity and type 2 diabetes (T2D) with cardiovascular risk. Composite surrogate indices derived from routine clinical parameters, such as the Metabolic Score for Insulin Resistance (METS-IR) and the Single Point Insulin Sensitivity Estimator (SPISE), may provide a practical means of capturing multidimensional metabolic changes. Given that comparative data are limited, we aimed to evaluate the effects of sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on these indices in individuals with T2D and overweight or obesity. Methods: In this retrospective observational study, 100 individuals with T2D treated with either GLP-1RA (n = 54) or SGLT2i (n = 46) were evaluated over 6 months. Strict inclusion criteria ensured treatment stability without initiation or modification of concomitant pharmacotherapy. Changes in METS-IR and SPISE were assessed alongside body mass index (BMI) and glycated hemoglobin (HbA1c). Multivariable regression and exploratory analyses, including stratification by BMI and correlation analyses, were performed. Results: Both treatment groups demonstrated significant improvements in METS-IR (GLP-1RA: −3.9 ± 5.9; SGLT2i: −2.5 ± 2.6; both p < 0.001) and SPISE (GLP-1RA: +0.46 ± 0.52; SGLT2i: +0.44 ± 0.61; both p < 0.001), with no significant between-group differences. In the GLP-1RA group, changes in METS-IR correlated with changes in BMI (r = 0.48, p < 0.001) and HbA1c (r = 0.29, p = 0.030), whereas no significant correlations were observed in the SGLT2i group. Stratified analyses indicated greater reductions in METS-IR among individuals with BMI ≥30 kg/m² treated with GLP-1RA. Conclusions: Both SGLT2i and GLP-1RA improve composite surrogate markers of insulin resistance, with distinct associations with weight and glycemic changes. METS-IR and SPISE may serve as practical tools for monitoring multidimensional metabolic responses in clinical practice. Full article

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin-based therapies has fundamentally transformed obesity pharmacotherapy, enabling magnitudes of non-surgical weight loss that were previously unattainable. Yet, the clinical success of these treatments cannot be measured in kilograms alone. Total body weight is a composite, tissue-nonspecific endpoint that fails to distinguish between adipose reduction and losses in skeletal muscle mass, strength, and physical function—compartments of direct relevance to metabolic health, functional independence, and long-term resilience. This narrative review builds on and extends existing conceptualizations of weight loss quality by proposing a clinically oriented, multidimensional framework of high-quality weight loss. Within this framework, preferential adiposity reduction is achieved while preserving skeletal muscle mass, neuromuscular function, dietary adequacy, and cardiometabolic health. We examine the physiological and clinical consequences of lean tissue loss during pharmacological energy restriction, with specific attention to phenotypes at greatest risk (i.e., older adults, individuals with sarcopenic obesity, and those with type 2 diabetes). We then evaluate the evidence supporting precision protein nutrition, dietary fiber adequacy, and gastrointestinal tolerability management as nutritional countermeasures, followed by a mechanistic and clinical analysis of resistance training as the primary exercise strategy for preserving lean mass and function. Finally, we discuss body composition monitoring, integrated multidisciplinary care, and unresolved research gaps. The future of obesity treatment lies not in greater weight loss per se, but in achieving better weight loss—defined as metabolically favorable, functionally responsible, and clinically sustainable. Bone health is treated as a further dimension of high-quality weight loss, since pharmacologically driven energy restriction can adversely affect areal bone mineral density and microarchitecture, and adequate protein intake combined with mechanical loading is required to preserve skeletal integrity alongside lean mass. Full article

Background/Objectives: Thoracic aortic aneurysm (TAA) often results from structural degeneration of the aortic wall. Traditional management focuses on hemodynamic control using beta-blockers (BB) and angiotensin receptor blockers (ARBs). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for diabetes and weight management, may offer additional vascular protective benefits through anti-inflammatory, antioxidative, and matrix-stabilizing mechanisms. However, their role in reducing mortality and thoracic aortic dissection (TAD) risk in patients with TAA has not been evaluated in human populations. In this study, we aimed to assess the association between GLP-1 RA use and the risks of mortality and thoracic aortic dissection. Methods: We conducted a retrospective cohort study of adults diagnosed with TAA between 2018 and 2024 across three Mayo Clinic sites. Patients receiving GLP-1 RAs were compared with non-users using 1:1 propensity score matching. Outcomes included all-cause mortality, cardiovascular mortality, and incident TAD. Kaplan–Meier and Cox proportional hazards analyses were performed. Results: A total of 32,279 patients with TAA, with a median age of 68.0 [IQR: 59.0–76.0] and 70.7% male, were included in a 1:1 propensity score match. This yielded a balanced cohort of 588 GLP-1 RA users and 588 non-users. Through a median follow-up of 4.1 (2.2, 5.9) years, GLP-1 RA use was associated with significantly lower 5-year cumulative incidence of all-cause mortality (5.0% vs. 14.5%, HR: 0.31; 95% CI: 0.19–0.50; p < 0.001), cardiovascular mortality (1.9% vs. 5.5%, HR: 0.30; 95% CI: 0.13–0.70; p = 0.005), and TAD (0.9% vs. 4.0%, HR: 0.19; 95% CI: 0.06–0.60; p < 0.0004). Conclusions: GLP-1 RAs are associated with reduced incidence of all-cause mortality, cardiovascular mortality, and TAD incidence in patients with TAA. Prospective studies are needed to confirm these findings and evaluate effects on aneurysm progression. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonist (GLP-1RA)- and incretin-based therapies are now central to obesity management. Their clinical value, however, should be interpreted beyond total weight loss, because changes in fat mass, lean mass, physical function, and cardiometabolic risk may depend on the accompanying dietary, behavioral, and exercise co-interventions. This systematic review and meta-analysis evaluated GLP-1RA- and incretin-based therapies delivered within lifestyle interventions in adults with overweight or obesity. Methods: The protocol was registered in PROSPERO (CRD420261360837). PubMed/MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, and CENTRAL were searched from inception to the final search dates. Records were deduplicated in Zotero. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analyses were estimated using restricted maximum likelihood with Hartung–Knapp adjustment when pooling was appropriate. Results: Across all database sources, 1651 records were identified. After removing 113 duplicate records and 212 records with an ineligible publication type before screening, 1326 records were screened. Seventy-seven reports were sought for retrieval, five were not retrieved, 72 were assessed at full text, and 48 reports corresponding to 35 independent parent trials or trial clusters were retained for qualitative synthesis. The primary kilogram-scale meta-analysis included eight independent comparisons and showed greater body-weight reduction with GLP-1RA/incretin-based therapy delivered within a lifestyle background than with placebo/control (mean difference [MD] −10.08 kg, 95% confidence interval [CI] −12.76 to −7.39; 95% prediction interval [PI] −17.86 to −2.29; I² = 95.6%). Percentage body-weight change was analyzed separately across 11 independent comparisons and also favored GLP-1RA/incretin-based therapy (MD −9.53 percentage points, 95% CI −11.92 to −7.14; 95% PI −17.58 to −1.48; I² = 95.4%). Conclusions: GLP-1RA- and incretin-based therapies delivered within lifestyle interventions are associated with clinically meaningful reductions in body weight in adults with overweight or obesity. Absolute and relative body-weight change metrics should remain analytically separate. The magnitude of benefit varies across trial contexts, and certainty remains limited by risk-of-bias concerns and considerable heterogeneity. Future trials should standardize the reporting of lifestyle co-interventions, body composition, adherence, physical-function outcomes, and safety monitoring. Full article

Background: With the increasing widespread use of GLP-1 RA and dual GIP/GLP-1 RAs in the treatment of obesity, their safety profile remains a concern for healthcare professionals (HPs). Objective: This study aimed to characterize and evaluate safety data from the EudraVigilance (EV) database for semaglutide (SEM), liraglutide (LIR), and tirzepatide (TIR). Methods: A hierarchical pharmacovigilance approach was applied, integrating SOC- and PT-level analyses with SmPC-based evaluation and both frequentist (ROR, 95% CI) and Bayesian (IC025) disproportionality methods. Within each molecule, reporter type–stratified analyses were performed, while across all molecules, disproportionality analyses were conducted separately in HP reports and in the full database to identify reporting patterns and potential safety signals, including those not described in the SmPCs. Results: Some ADRs, listed in the SmPC of only one or two of the three GLP1-RAs were also reported in the EV database for the other agents whose SmPCs do not specify these ADRs including optic ischemic neuropathy (TIR: 0.28% and LIR: 0.17%), alopecia (LIR: 0.81%), headache (TIR: 2.51%), intestinal obstruction (TIR: 1.55%), angioedema (LIR: 0.19%), hypersensitivity (SEM: 0.58% and LIR: 0.73%), etc. Pancreatitis, in particular, showed a significant but low-magnitude signal, being more frequently reported by HPs compared with non-HPs across all three GLP1-RAs. Additionally, statistically significant signals (IC025 > 0) were observed in both the HPs and full datasets. For example, for SEM vs. TIR, signals were identified for optic ischemic neuropathy (0.17; 0.13), gallbladder disorder (0.09; 0.11), and dysesthesia (0.42; 0.43), respectively. For TIR vs. SEM, signals were observed for injection site erythema (0.05; 0.11), injection site pruritus (0.01; 0.11), and injection site reaction (0.02; 0.08). Conclusions: These findings suggest potential safety signals beyond current SmPC information, emphasizing the need for continuous pharmacovigilance and cautious interpretation of reporting biases. Full article

Introduction: Obesity is a chronic, multifactorial disease associated with significant metabolic and cardiovascular complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective pharmacological options for weight management, demonstrating clinically relevant weight loss in controlled trials. However, real-world evidence is essential to assess their effectiveness and safety under routine clinical conditions and to verify if trial results are reproducible in diverse populations. Objective: We aimed to evaluate the effectiveness and safety of GLP-1RAs in terms of weight loss in real-world clinical practice and to compare outcomes among different available agents, focusing on their impact on obesity management. Method: A cross-sectional, observational pilot study was conducted in Spain. Adult patients receiving GLP-1RAs for at least four weeks were included. Data collected included sociodemographic variables, treatment characteristics, anthropometric measurements, and adverse effects. Weight loss outcomes were analyzed using descriptive statistics, ANOVA for inter-drug comparisons, and multivariate ANCOVA to adjust for confounders. This pilot study also validated the protocol for a subsequent nationwide multicenter study. Results: A total of 32 patients (62.5% women; mean age 58.2 years) were analyzed. Mean weight loss was 2.97 kg (3.17%). Significant differences between drugs were observed (p = 0.005), with semaglutide 2.4 mg (Wegovy^®) showing the greatest weight reduction (11.0 kg). Patients without diabetes achieved significantly greater weight loss than those with diabetes (5.0 vs. 0.8 kg; p = 0.021). Treatments were well tolerated, with 53.1% reporting no adverse effects; most side effects were mild gastrointestinal symptoms. Conclusions: GLP-1RAs are effective and well-tolerated for obesity treatment in real-world clinical practice, although weight loss is more modest than in pivotal clinical trials. Differences between agents were observed after multivariate adjustment, although these findings should be interpreted cautiously given the exploratory pilot design and limited sample size. These findings support the need for individualized treatment strategies in obesity care. This pilot study successfully validated the methodology for an ongoing nationwide investigation. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed type 2 diabetes mellitus (T2DM) and obesity care, with clinical trials demonstrating weight loss exceeding 15%. However, real-world effectiveness lags trial efficacy, largely owing to high discontinuation rates. We characterize the global persistence gap and propose a framework integrating Medical Nutrition Therapy (MNT) to improve adherence. Methods: We conducted a narrative review of real-world evidence from North America, Europe, Asia, and Latin America, synthesized with physiological, nutritional, and behavioral data to distinguish established contributors to discontinuation from strategies that remain partly extrapolated from related populations. Results: Global persistence varies widely: from approximately 75–80% at 12 months in reimbursed T2DM cohorts (Sweden, Denmark) to below 10% in obesity-focused or high out-of-pocket-cost settings (Poland, Colombia), with intermediate rates in the United States and United Kingdom; in several cohorts, persistence falls below 15% by 24 months. The primary drivers are gastrointestinal intolerance and economic barriers. Meal size, dietary composition, and gastric-emptying effects influence gastrointestinal tolerability; inadequate protein intake during rapid weight loss raises concern for lean mass loss. Conclusions: Pharmacotherapy alone is unlikely to sustain long-term obesity management. Narrowing the persistence gap will require an integrated care model in which structured nutritional support—targeting protein intake, micronutrient density, and gastric-sparing feeding—is systematically offered rather than treated as an optional adjunct, while recognizing that most supporting evidence is extrapolated from primary trials in obesity and cardiometabolic disease rather than derived from GLP-1–specific randomized trials. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed obesity treatment, producing substantial weight loss during active therapy. However, real-world effectiveness may be limited by gastrointestinal adverse events, reduced dietary intake, fat-free mass loss as part of total weight reduction, and weight regain after discontinuation. Methods: This narrative review synthesizes current pharmacological, nutritional, gastrointestinal, body-composition, and implementation evidence to propose an evidence-informed nutrition-first framework for patients receiving incretin-based therapy for obesity. Results: We translate pharmacologic mechanisms into practical dietary strategies, including protein prioritization, structured meal patterns, hydration and fiber management, symptom-targeted interventions, resistance-training support, and maintenance planning. Because direct trials of structured nutrition interventions in GLP-1RA- or dual incretin-treated populations remain limited, several recommendations are extrapolated from the broader obesity, caloric restriction, body-composition, gastrointestinal, and expert-consensus literature. Conclusions: Integrating structured nutrition care into pharmacotherapy pathways may help address meal-related symptom burden, support protein and fluid adequacy, identify patients at higher nutritional or body-composition risk, and prepare patients for long-term weight-management behaviors. Embedding practical nutrition management within multidisciplinary obesity care may help translate pharmacologic efficacy into durable, patient-centered outcomes. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now recognized as the principal hepatic manifestation of obesity and metabolic dysfunction. Its pathogenesis is complex and multifactorial, driven by insulin resistance, low-grade chronic inflammation, oxidative stress, gut microbiota alterations, and abnormalities in lipid metabolism; together, these promote steatosis, lipotoxicity, and progression to fibrosis which can lead to compensated advanced chronic liver disease (cACLD). MASLD is also a multisystem condition closely associated with an increased risk of major adverse cardiovascular events such as myocardial infarction, ischemic stroke, atrial fibrillation, and other extrahepatic complications. In this context, emerging metabolic therapies show significant potential for modifying the natural history of the disease. Glucagon-like peptide (GLP)-1 receptor agonists induce substantial weight loss and improve steatosis and necro-inflammatory activity. Sodium–glucose cotransporter 2 inhibitors (SGLT-2I) reduce glucotoxicity, promote modest weight loss, and lower hepatic fat content by improving insulin sensitivity and inflammatory signaling. Even more promising are dual GLP-1/GIP receptor agonists, which have demonstrated superior efficacy in metabolic control, reducing hepatic steatosis, and potentially modulating fibrotic processes, although definitive histological confirmation is still lacking. Overall, in this review, we discuss the physiopathological mechanisms of MASLD leading to cACLD along with the emerging therapies, such GLP1 receptor agonists, SGLT-2I, and GLP1/GIP which, when combined with structured lifestyle interventions, may attenuate progression toward steatohepatitis (MASH), fibrosis, and, thus, cirrhosis. Full article