Search Results (623)

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide, arising from complex interactions among metabolic, genetic, and environmental factors. Nicotinamide N-methyltransferase (NNMT) has recently emerged as a key metabolic regulator in CVD pathogenesis. By consuming nicotinamide and methyl groups, NNMT perturbs epigenetic, metabolic, and redox pathways that are critical for cardiovascular health. NNMT-mediated NAD⁺ depletion impairs mitochondrial function, sirtuin (SIRT) activity, redox balance, and energy metabolism, thereby creating a pro-atherogenic environment. NNMT and its product 1-methylnicotinamide (1-MNA) show a complex duality: they modulate SIRT activity—particularly SIRT1 and SIRT3—to influence gluconeogenesis, cholesterol synthesis, lipogenesis, and mitochondrial antioxidant defenses. NNMT upregulation also elevates homocysteine levels, activating pro-inflammatory and pro-oxidative cascades (e.g., TLR4–NF-κB and STAT3–IL-1β). Growing evidence links NNMT to major CVD risk factors, including hyperlipidemia, hypertension, diabetes mellitus, and obesity. Thus, NNMT has a multifaceted role in cardiovascular health: while its enzymatic activity is often pathogenic (via NAD⁺/SAM consumption and homocysteine production), its metabolite 1-MNA can exert protective effects (via NRF2 activation and anti-thrombotic mechanisms). This duality highlights the need to delineate the molecular processes that balance these opposing actions. Experimental studies using small-molecule NNMT inhibitors and RNA interference have shown promising cardiometabolic benefits in preclinical models, including improved insulin sensitivity, reduced atherosclerosis, and attenuated cardiac dysfunction. However, no clinical trials have yet targeted NNMT specifically in CVD. Future research should clarify the tissue-specific functions of NNMT and translate these insights into novel therapeutic strategies. Full article

Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) profoundly disrupt lipid metabolism within local microenvironments of skeletal muscle and its associated connective tissues, including adipose tissue, bone, and fascia. However, the role of local communication between skeletal muscle and its proximal connective tissues in propagating metabolic dysfunction is incompletely understood. This narrative review synthesizes current evidence on these local metabolic interactions, highlighting novel insights and existing gaps. Methods: We conducted a comprehensive literature analysis of primary research published in the last decade, sourced from PubMed, Web of Science, and ScienceDirect. Studies were selected for relevance to skeletal muscle, adipose tissue, fascia, and bone lipid metabolism in the context of obesity and T2DM, with emphasis on molecular, cellular, and paracrine mechanisms of local crosstalk. Findings were organized into thematic sections addressing physiological regulation, pathological remodeling, and inter-organ signaling pathways. Results: Our synthesis reveals that local lipid dysregulation in obesity and T2DM involves altered fatty acid transporter dynamics, mitochondrial overload, fibro-adipogenic remodeling, and compartment-specific adipose tissue dysfunction. Crosstalk via myokines, adipokines, osteokines, bioactive lipids, and exosomal miRNAs integrates metabolic responses across these tissues, amplifying insulin resistance and lipotoxic stress. Emerging evidence highlights the underappreciated roles of fascia and marrow adipocytes in regional lipid handling. Conclusions: Collectively, these insights underscore the pivotal role of inter-tissue crosstalk among skeletal muscle, adipose tissue, bone, and fascia in orchestrating lipid-induced insulin resistance, and highlight the need for integrative strategies that target this multicompartmental network to mitigate metabolic dysfunction in obesity and T2DM. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic lipid accumulation and insulin resistance, yet effective therapies remain limited. This study evaluated the hepatoprotective effects of Desmodium caudatum (Thunb.) DC. Extract (DCE) in vitro and in vivo. In 600 μM oleic acid (OA)-challenged HepG2 cells, DCE (25, 50, and 100 μg/mL) reduced lipid accumulation, oxidative stress, and glycogen depletion by modulating lipogenic and oxidative pathways. In a MASLD mouse model induced by high-fat diet (HFD)/streptozotocin (HFD/STZ), oral administration of DCE (100 or 200 mg/kg) for six weeks improved fasting glucose, serum lipids, and hepatic injury markers. Histology confirmed reduced steatosis, while Western blotting showed downregulation of SREBP-1, HMGCR, and ACC, and upregulation of CPT-1, PPARα, and phosphorylated AMPK. Additionally, DCE enhanced insulin signaling and restored hepatic glycogen synthesis through IRS-1, AKT, and GSK3β activation. These findings suggest that DCE ameliorates MASLD by regulating lipid and glucose metabolism, supporting its potential as a plant-based therapeutic strategy. Full article

Fish reproduction requires suitable salinity and temperature, as well as sufficient energy. This study investigated temperature and salinity effects on ovarian development of Lateolabrax maculatus and energy metabolism differences between reproduction and growth. Two salinities (4‰ and 30‰) and temperatures (18 ± 1 °C and 30 ± 1 °C) formed four treatments: SWNT (30‰, 30 ± 1 °C), SWLT (30‰, 18 ± 1 °C), FWLT (4‰, 18 ± 1 °C), and FWNT (4‰, 30 ± 1 °C). GSI and sex hormones (FSH, LH, E2, and 17α,20β-DHP) were measured. Transcriptome analysis explored how temperature and salinity regulate ovarian development in L. maculatus, while integrated transcriptomic and targeted energy metabolomic analyses revealed energy metabolism differences between ovary and muscle during this process. The results showed that low salinity (4‰) and low temperature (18 ± 1 °C) synergistically promoted ovarian development in the FWLT group, as indicated by a significant increase in GSI and elevated levels of key sex hormones (FSH, LH, E2, and 17α,20β-DHP). Transcriptome analysis showed that low temperature activated pathways involved in steroidogenesis, oocyte maturation, and meiosis, and genes such as ADCY6, PRKACB, CPEB4, FZD7-A, and CCND2 were significantly upregulated. Salinity changes mainly affected amino acid metabolism, cholesterol metabolism, and the insulin signaling pathway. Genes such as PCSK9 and CKM may regulate ovarian development by regulating hormone synthesis and energy metabolism. Comprehensive transcriptome and metabolome analyses show that glycolysis is downregulated and oxidative phosphorylation is upregulated in the ovary, suggesting that ovarian oogenesis tends to be energized by aerobic metabolism. The TCA cycle may be used more for providing biosynthetic precursors and facilitating the transport of substrates between the mitochondrion and the cytoplasm rather than just as a source of ATP. Muscle tissue relies primarily on glycolysis for rapid energy production and may redistribute energy to the gonads, prioritizing the energy needs of the ovaries and contributing to the dynamic balance between reproduction and growth. This study provides insights into the molecular mechanisms of how environmental factors regulate fish reproduction, providing a theoretical basis and potential molecular targets for the regulation of reproduction and optimization of aquaculture environments. Full article

Cardiometabolic diseases such as obesity, prediabetes (PreD), and type 2 diabetes (T2D) are global health challenges linked to metabolic dysfunction. While probiotics show promise, postbiotics offer advantages in stability, safety, and food incorporation. This study evaluates the postbiotic pA1c^®HI, a heat-inactivated form of the probiotic pA1c^®, for its potential in modulating glucose and lipid metabolism in Caenorhabditis elegans, compared to its live form. Worms were supplemented with pA1c^®HI and live pA1c^® in glucose-enriched media. Fat accumulation, gene expression, oxidative stress, and lifespan were measured using Nile Red and DHE staining, qPCR, and longevity assays. pA1c^®HI significantly reduced glucose-induced fat accumulation, achieving fat reduction comparable to the anti-obesity drug orlistat and showing superior efficacy compared to the live probiotic form. It modulated the expression of genes associated with lipid oxidation (acox-1, cpt-2), fatty acid synthesis (fat-5), insulin signaling (daf-2, daf-16), and oxidative stress response (skn-1). Synergistic combinations with chromium picolinate (PC) and zinc (Zn) further enhanced metabolic outcomes. Importantly, pA1c^®HI retained efficacy after thermal treatment (121–135 °C), supporting its potential for use in processed foods. pA1c^®HI is a stable, effective postbiotic that modulates key pathways associated with obesity, PreD, and T2D in C. elegans, with superior performance to the live probiotic and added benefits when combined with PC and Zn. Full article

Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic organs. The gut hosts trillions of microbes and enteroendocrine cells that influence inflammation, energy homeostasis, and hormone regulation. Disruptions in gut homeostasis (dysbiosis and increased permeability) have been linked to obesity, insulin resistance, and β-cell dysfunction, suggesting multifaceted “Gut-X axes” contribute to T2D development. We aimed to comprehensively review the evidence for gut-mediated crosstalk with the pancreas, endocrine system, liver, and kidneys in T2D. Key molecular mechanisms (incretins, bile acids, short-chain fatty acids, endotoxins, etc.) were examined to construct an integrated model of how gut-derived signals modulate metabolic and inflammatory pathways across organs. We also discuss clinical implications of targeting Gut-X axes and identify knowledge gaps and future research directions. A literature search (2015–2025) was conducted in PubMed, Scopus, and Web of Science, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews). Over 150 high-impact publications (original research and review articles from Nature, Cell, Gut, Diabetologia, Lancet Diabetes & Endocrinology, etc.) were screened. Data on gut microbiota, enteroendocrine hormones, inflammatory mediators, and organ-specific outcomes in T2D were extracted. The GRADE framework was used informally to prioritize high-quality evidence (e.g., human trials and meta-analyses) in formulating conclusions. T2D involves perturbations in multiple Gut-X axes. This review first outlines gut homeostasis and T2D pathogenesis, then dissects each axis: (1) Gut–Pancreas Axis: how incretin hormones (GLP-1 and GIP) and microbial metabolites affect insulin/glucagon secretion and β-cell health; (2) Gut–Endocrine Axis: enteroendocrine signals (e.g., PYY and ghrelin) and neural pathways that link the gut with appetite regulation, adipose tissue, and systemic metabolism; (3) Gut–Liver Axis: the role of microbiota-modified bile acids (FXR/TGR5 pathways) and bacterial endotoxins in non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; (4) Gut–Kidney Axis: how gut-derived toxins and nutrient handling intersect with diabetic kidney disease and how incretin-based and SGLT2 inhibitor therapies leverage gut–kidney communication. Shared mechanisms (microbial SCFAs improving insulin sensitivity, LPS driving inflammation via TLR4, and aryl hydrocarbon receptor ligands modulating immunity) are synthesized into a unified model. An integrated understanding of Gut-X axes reveals new opportunities for treating and preventing T2D. Modulating the gut microbiome and its metabolites (through diet, pharmaceuticals, or microbiota therapies) can improve glycemic control and ameliorate complications by simultaneously influencing pancreatic islet function, hepatic metabolism, and systemic inflammation. However, translating these insights into clinical practice requires addressing gaps with robust human studies. This review provides a state-of-the-art synthesis for researchers and clinicians, underlining the gut as a nexus for multi-organ metabolic regulation in T2D and a fertile target for next-generation therapies. Full article

The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing enzymes, transporters, inflammatory factors, lipid metabolism, and immune-related pathways, contributing to the maintenance of hepatic–intestinal barrier homeostasis, energy metabolism, and inflammatory responses. Specifically, in type 2 diabetes mellitus (T2DM), PXR influences disease progression by regulating glucose metabolism and insulin sensitivity. In obesity, it affects adipogenesis and inflammatory processes. In atherosclerosis (AS), PXR exerts protective effects through cholesterol metabolism and anti-inflammatory actions. In metabolic dysfunction-associated steatotic liver disease (MASLD), it is closely associated with lipid synthesis, oxidative stress, and gut microbiota balance. Moreover, PXR plays dual roles in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Currently, PXR-targeted strategies, such as small molecule agonists and antagonists, represent promising therapeutic avenues for treating metabolic diseases and cancer. This review comprehensively summarizes the structural features, signaling pathways, and gene regulatory functions of PXR, as well as its role in metabolic diseases and cancer, providing insights into its therapeutic potential and future drug development challenges. Full article

Background: The rate at which amino acids (AAs) are absorbed from casein glycomacropeptide (CGMP) when given as a protein substitute in phenylketonuria (PKU) is unknown. This three-way randomised, controlled, crossover study aimed to compare the AA absorption profile of phenylalanine (Phe)-free L-amino acids (L-AAs), low-Phe CGMP (CGMP) and casein in healthy adult subjects. Methods: Area under the curve (AUC) was measured over 240 minutes after ingesting one dose of each protein source on three separate occasions, under the same test conditions. A total of 0.4 g/kg protein equivalent of each test product (L-AA, CGMP and casein) was given. Fasted blood samples were collected from healthy volunteers at 30, 60, 90, 120, 150, 180 and 240 minutes post-test. Insulin, blood urea nitrogen, glucose and total (TAAs), essential (EAAs), large neutral (LNAAs) and branch chain (BCAAs) amino acids were measured at each time point. Results: A total of 20 subjects (11 females), median age 43 y (range 23–49), with a median BMI 24.2 (20–30.5) were recruited. AUC was compared across groups. Statistically significant differences were noted for: AUC for TAAs and BCAAs between CGMP and L-AAs vs. casein [TAAs p = 0.008 and p = 0.03; BCAAs p = <0.001 and p = 0.002]. There were no AUC differences between L-AAs and CGMP. AUC was largest for L-AAs, then CGMP and finally casein. For LNAAs, EAAs, insulin, glucose and urea, there were no statistically significant differences. There was a consistent delivery of AAs for casein demonstrated by a sustained curve, but the absorption curves for L-AAs and CGMP were transient, rising rapidly and falling, with the exception of tyrosine with CGMP which showed a gradual increase over 240 minutes in contrast to L-AAs and casein. Conclusions: Amino acids from CGMP and L-AAs were absorbed more rapidly than casein, inferring CGMP did not mimic casein, a slow-release protein source. The tyrosine concentration curve for CGMP suggests a beneficial effect on the Phe: tyrosine ratio. Kinetic labelled studies will help bring greater understanding on the utilisation of AAs particularly important for protein synthesis. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic hepatopathy and a leading precursor of hepatocellular carcinoma (HCC) worldwide. Initially attributed to insulin resistance (IR)-driven metabolic imbalance, recent insights highlight a multifactorial pathogenesis involving oxidative stress (OS), chronic inflammation, and immune dysregulation. The hepatic accumulation of free fatty acids (FFAs) initiates mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, culminating in lipotoxic intermediates and mitochondrial DNA damage. These damage-associated molecular patterns (DAMPs), together with gut-derived pathogen-associated molecular patterns (PAMPs), activate innate immune cells and amplify cytokine-mediated inflammation. Kupffer cell activation further exacerbates OS, while ROS-induced transcriptional pathways perpetuate inflammatory gene expression. Traditional immunity refers to the well-established dichotomy of innate and adaptive immune responses, where innate immunity provides immediate but non-specific defense, and adaptive immunity offers long-lasting, antigen-specific protection. However, a paradigm shift has occurred with the recognition of trained immunity (TI)—an adaptive-like memory response within innate immune cells that enables enhanced responses upon re-exposure to stimuli. Following non-specific antigenic stimulation, TI induces durable epigenetic and metabolic reprogramming, leading to heightened inflammatory responses and altered functional phenotypes. These rewired cells acquire the capacity to produce lipid mediators, cytokines, and matrix-modifying enzymes, reinforcing hepatic inflammation and fibrogenesis. In this context, the concept of immunometabolism has gained prominence, linking metabolic rewiring with immune dysfunction. This literature review provides an up-to-date synthesis of emerging evidence on immunometabolism and trained immunity as pathogenic drivers in MASLD. We discuss their roles in the transition from hepatic steatosis to steatohepatitis, fibrosis, and cirrhosis, and explore their contribution to the initiation and progression of MASLD-related HCC. Understanding these processes may reveal novel immunometabolic targets for therapeutic intervention. Full article

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics. Full article

Background: Aluminum accumulation in the brain causes cognitive deficits. No comprehensive synthesis of pharmacological treatments against aluminum neurotoxicity has been conducted, which led us to systematically review the effects of various pharmacological agents against aluminum-induced neurotoxicity, primarily addressing learning and memory after chronic aluminum exposure (≥2 months) in rodent models. Methods: A literature search was performed in PubMed, Google Scholar, Science Direct, and Scopus for studies published between 2000 and 2023. A total of 45 studies were selected according to the inclusion criteria. Primary outcomes focused on assessing learning and memory, with 39 different pharmacological agents evaluated explicitly for their effects against aluminum-induced neurotoxicity. Meta-analysis and subgroup analysis were performed to evaluate cognitive improvement in the Morris water maze (MWM) for learning and memory, and oxidative stress parameters were evaluated through superoxide dismutase (SOD) and catalase (CAT) in aluminum-induced neurotoxicity models. Results: According to the systematic analysis, most treatments significantly improve learning and memory, except for insulin and melatonin. According to the MWM analysis, Memantine, Hypericum perforatum extract, Bennincasa hespidia, and, based on the biochemical analysis, Chrysin showed better results. The meta-analysis (random effects) revealed reduced escape latency (SMD = 0.97, 95% CI: 0.74 to 1.19) and increased SOD (SMD = −0.54, 95% CI: −0.79 to −0.29) and CAT levels (SMD = −0.50, 95% CI: −0.73 to −0.27) in treated groups versus aluminum. Egger’s regression tests showed no strong evidence of publication bias. Conclusions: This study effectively synthesized preclinical evidence, identifying promising pharmacological agents for mitigating aluminum-induced cognitive deficits. These findings offer a scientific basis for future experimental studies and therapeutic development targeting aluminum neurotoxicity. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant (p < 0.01) decrease in oxidative stress by 83%, and a marked (p < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes. Full article

Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination and their relevance to metabolic health. We examined recent in vitro, animal, and human studies focusing on how germination enhances the nutritional and functional properties of grains, particularly through the synthesis of compounds such as γ-aminobutyric acid, polyphenols, flavonoids, and antioxidants, while reducing anti-nutritional factors. These bioactive compounds have been shown to modulate metabolic and inflammatory pathways by inhibiting carbohydrate-digesting enzymes, suppressing pro-inflammatory cytokines, improving redox balance, and influencing gut microbiota composition. Collectively, these effects contribute to improved insulin sensitivity and glycemic control. The findings suggest that sprouted grains serve not only as functional food ingredients but also as accessible dietary tools for preventing or alleviating IR. Their role in delivering multiple bioactive molecules through a simple, environmentally friendly process highlights their promise in developing future nutrition-based strategies for metabolic disease prevention. Full article

Childhood obesity increases chronic disease risk, but no comprehensive synthesis has evaluated the impact of school-based combined nutrition education and physical activity interventions on cardiometabolic biomarkers in children aged 3 to 12 years. This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251085194). Five databases were systematically searched through June 2025. Twelve randomized controlled trials involving 18,231 children were included and assessed using the PEDro scale. Ten trials demonstrated significant improvements in at least one cardiometabolic biomarker. Blood pressure (8 studies) outcomes showed systolic reductions of 1.41–6.0 mmHg in six studies. Glucose metabolism (5 studies) improved in two studies with reductions of 0.20–0.22 mmol/L. Lipid profiles (7 studies) improved in three studies, including total cholesterol (−0.32 mmol/L). Insulin levels (5 studies) decreased significantly in two investigations. Anthropometric improvements included BMI and body fat. Physical activity increased by >45 min/week and dietary habits improved significantly. Programs with daily implementation (90-min sessions 4x/week), longer duration (≥12 months), family involvement (parent education), and curriculum integration (classroom lessons) showed superior effectiveness. Interventions targeting children with overweight/obesity demonstrated higher changes compared to the general population. However, methodological limitations included a lack of assessor blinding, absence of subject/therapist blinding, and inadequate retention rates. School-based interventions combining nutrition and physical activity can produce significant improvements in cardiometabolic biomarkers, supporting comprehensive, sustained multicomponent programs for early chronic disease prevention. Full article

Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits. Full article