Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins that regulate postprandial glucose regulation, stimulating insulin secretion from pancreatic β-cells in response to food ingestion. Modified GLP-1 receptor agonists (GLP-1RAs) are being administered for the treatment of obesity and type 2 diabetes mellitus (T2DM). Strongly related to those disorders, metabolic dysfunction-associated steatotic liver disease (MASLD), especially its aggressive form, defined as metabolic dysfunction-associated steatohepatitis (MASH), is a major healthcare burden associated with high morbidity and extrahepatic complications. GLP-1RAs have been explored in MASH patients with evident improvement in liver dysfunction enzymes, glycemic control, and weight loss. Importantly, the combination of GLP-1RAs with GIP and/or glucagon RAs may be even more effective via synergistic mechanisms in amelioration of metabolic, biochemical, and histological parameters of MASLD but also has a beneficial impact on MASLD-related complications. In this current review, we aim to provide an overview of incretins’ physiology, action, and signaling. Furthermore, we provide insight into the key pathophysiological mechanisms through which they impact MASLD aspects, as well as we analyze clinical data from human interventional studies. Finally, we discuss the current challenges and future perspectives pertinent to this growing area of research and clinical medicine.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and newer incretin-based co-agonists have transformed obesity and type 2 diabetes (T2D) management, achieving unprecedented weight loss and cardiometabolic benefits. However, their effects on body composition, particularly lean and skeletal muscle mass, remain incompletely defined. In this current review, we examined the influence of GLP-1 RAs and incretin hormone agonists on lean tissue, integrating physiological, clinical, and mechanistic perspectives. We first outlined the physiology of incretin hormones, with emphasis on their metabolic roles and potential relevance to muscle health. We then discussed sarcopenia and sarcopenic obesity as conditions of rising clinical concern, given their overlap with obesity and metabolic disease. Evidence from preclinical studies and randomized clinical trials indicates that while GLP-1-based therapies predominantly reduce adipose tissue, including visceral and ectopic depots, but they also produce absolute reductions in lean mass, generally representing 20–30% of total weight loss. The extent to which these changes translate into impaired muscle function or increased vulnerability to frailty remains unclear. Preservation of lean and skeletal muscle mass is a critical yet underexplored aspect of incretin-based weight loss. Current studies are constrained by methodological heterogeneity, small sample sizes, and limited assessment of functional outcomes. Data on dual and triple agonists are emerging but remain limited. Future research should integrate standardized body-composition measures, mechanistic exploration, and adjunctive interventions such as resistance training or protein optimization.

Osteoporosis is a major complication of thalassemia bone disease, leading to increased fracture risk and impaired quality of life. Anti-resorptive agents, such as bisphosphonates and denosumab, have shown efficacy in randomized trials, but data are scarce, regarding the role of anabolic agents in severe cases with fragility fractures. We report 2 cases with severe osteoporosis associated to thalassemia with multiple vertebral and non-vertebral fractures, despite long term-treatment with anti-resorptive agents. Both patients were initiated on subcutaneous romosozumab (210 mg once monthly) for 12 mo. At 12 mo, BMD showed marked improvement at the LS by 6.8%-15.4%, TH by 14.6%, and FN by 8.7%-24.6%. Bone turnover markers changed in line with clinical trials of postmenopausal osteoporosis. No adverse events occurred during the treatment period. Following completion of romosozumab therapy, each patient received a single infusion of zoledronate to consolidate the bone mass gained. Over 24 mo follow-up, no new fragility fractures were observed. Romosozumab can be an effective and safe anabolic option for patients with thalassemia and high fracture risk. While anti-resorptive therapy remains the standard of care, romosozumab may provide additional benefit in thalassemia patients with severe osteoporosis and increased fracture risk.

The causal link between dyslipidemia and cardiovascular disease (CVD) is well-established. Data, however, on the epidemiology and the extent of lipid-lowering treatment (LLT) in the general population are limited. We used the national electronic prescribing database (IDIKA), embracing almost all prescriptions issued in Greece, to capture individuals who received LLT during 2021. The study population included all 8,535,780 adults (≥20 years) in Greece in 2021. The overall prevalence of LLT accounted for the 23.4% of the adult Greek population (n=1,997,341), being higher in women than in men (23.9% vs 22.8%, respectively, p<0.001). It gradually increased with age with a maximum rate of 56.1% observed in the 70-79 age group. That year, 245,660 adults (n=121,630 men and 124,030 women) were prescribed LLT for the first time, accounting for an incidence rate of 3.6%, with a slight predominance of males compared to females (3.7% vs 3.6%, respectively, p<0.001). Most common concomitant diseases reported were arterial hypertension (45.7%), type 2 diabetes (28.4%), and coronary artery disease (14.4%). General practitioners (33.7%), internists (33.7%) and cardiologists (21.6%) were the primary prescribers. Rosuvastatin and atorvastatin were the most prescribed statins accounting for approximately 60% of prescriptions. Ezetimibe and fenofibrate were prescribed in 18% and 4%, respectively, as monotherapy or combination therapy. Approximately 23% of the adult Greek population was prescribed LLT, mainly statins, during 2021, with an annual incidence rate of 3.6% in this first nation-wide study in Greece. Large-scale reports from electronic prescription databases are warranted to improve public health strategies.

Background/Objectives: Omentin, also known as intelectin-1, is a secreted adipokine with anti-inflammatory, insulin-sensitizing, and immune-modulatory functions, primarily expressed in visceral adipose tissue. While omentin has been associated with favorable metabolic outcomes, its role in cancer pathogenesis appears context-dependent and remains poorly understood. This review investigates the biological functions, expression patterns, and clinical relevance of omentin across gastrointestinal malignancies. Methods: A comprehensive review of the literature was conducted using PubMed, Scopus, and Web of Science up to August 2025 to evaluate the role of omentin in gastrointestinal cancers. Both preclinical and clinical studies evaluating omentin, its analogues and omentin-enhancing agents in gastric, colorectal, hepatic, pancreatic, and esophageal cancers were included. Results: Omentin exhibits anti-proliferative, anti-inflammatory, and anti-angiogenic effects within the tumor microenvironment in several GI malignancies. However, evidence also indicates a dual role. High intratumoral omentin expression correlates with improved prognosis in colorectal, gastric, and hepatic cancers; in contrast, elevated circulating levels–particularly in colorectal and pancreatic cancers–have been paradoxically associated with increased cancer risk and poor outcomes. Mechanistically, omentin modulates PI3K/Akt, NF-κB, AMPK, and oxidative stress pathways, and interacts with TMEM207. However, most available studies are small-scale and heterogeneous, with methodological inconsistencies and limited multi-omics integration, leaving major knowledge gaps. Conclusions: This review highlights omentin’s distinct systemic and local roles across GI cancers, underscoring its translational implications. Omentin emerges as a promising but context-dependent biomarker and therapeutic target, with future research needed to address heterogeneity, standardize assays, and validate its clinical utility in large-scale prospective studies.