Hypouricemic effect of sodium glucose transporter-2 inhibitors: a Network Meta-analysis and Meta-regression of Randomized Clinical Trials

Expert Review of Endocrinology & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are known for their cardiovascular benefits, but impact on serum uric acid levels is not well understood. This study evaluates the hypouricemic effects of SGLT2is and potential implications. A network meta-analysis was performed, including 56 studies (16,788 participants) contributing data to meta-analysis. The were analyzed with weighted mean difference (WMD) as effect estimate. Bootstrapped meta-analysis, trial sequential analysis, meta-regression utilized validate findings assess influence covariates. certainty evidence evaluated. analysis revealed that significantly reduced (WMD: -40.01 μmol/L). Specific reductions noted ertugliflozin (-42.17 μmol/L), dapagliflozin (-40.28 empagliflozin (-46.75 canagliflozin (-35.55 ipragliflozin (-10.48 Both low high doses effective, showing highest efficacy. No significant associations found moderate certainty. lower levels, being most effective. These suggest a role in reducing risk. Further research needed explore hyperuricemic patients, monitoring recommended.

Language: Английский

---

Anti-Inflammatory Effects of SGLT2 Inhibitors: Focus on Macrophages

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1670 - 1670

Published: Feb. 15, 2025

A growing body of evidence indicates that nonglycemic effects sodium-glucose cotransporter 2 (SGLT2) inhibitors play an important role in the protective these drugs diabetes, chronic kidney disease, and heart failure. In recent years, anti-inflammatory potential SGLT2 has been actively studied. This review summarizes results clinical experimental studies on activity inhibitors, with a special focus their macrophages, key drivers metabolic inflammation. patients type therapy reduces levels inflammatory mediators. diabetic non-diabetic animal models, control low-grade inflammation by suppressing activation tissue recruitment monocytes from bloodstream, macrophage polarization towards M1 phenotype. The molecular mechanisms macrophages include attenuation inflammasome inhibition TLR4/NF-κB pathway, as well modulation other signaling pathways (AMPK, PI3K/Akt, ERK 1/2-MAPK, JAKs/STAT). discusses state-of-the-art concepts prospects further investigations are needed to obtain deeper insight into underlying molecular, cellular, physiological levels.

Language: Английский

---

Risk of Serious Bacterial and Non‐Bacterial Infections in People With MASLD

Liver International, Journal Year: 2025, Volume and Issue: 45(4)

Published: March 12, 2025

ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) has become the most common chronic globally. MASLD is a multisystem where metabolic dysfunction plays key role in development of and its relevant liver‐related morbidities extrahepatic complications, such as cardiovascular disease, kidney certain types cancers. Among least examined MASLD‐related an ever‐increasing number observational studies have reported positive association between risk serious bacterial infections (SBI) requiring hospital admission. This remained significant those statistical analysis was adjusted for age, sex, ethnicity, obesity, type 2 diabetes other comorbidities. Notably, incidence rates SBI were further increased with more advanced MASLD, especially patients cirrhosis, also observed some acute viral infections, including SARS‐CoV‐2 infection, leading to severe COVID‐19. In this narrative review article, we provide overview literature on (a) recent epidemiological data linking non‐bacterial admission, (b) putative underlying mechanisms through which may increase susceptibility both directly immune associated cirrhosis portal hypertension, (c) practical clinical implications growing global population MASLD.

Language: Английский

---

Advancements in the Research of Non-Immunosuppressive Therapies for Chronic Kidney Disease

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(01), P. 2193 - 2202

Published: Jan. 1, 2025

Language: Английский

---

A Narrative Review of the Interplay between Carbohydrate Intake and Diabetes Medications: Unexplored Connections and Clinical Implications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 624 - 624

Published: Jan. 13, 2025

This narrative review examines the dynamic interplay between carbohydrate intake and diabetes medications, highlighting their combined molecular clinical effects on glycemic control. Carbohydrates, a primary energy source, significantly influence postprandial glucose regulation necessitate careful coordination with pharmacological therapies, including insulin, metformin, glucagon-like peptide (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors. Low-glycemic-index (GI) foods enhance insulin sensitivity, stabilize variability, optimize medication efficacy, while high-GI exacerbate excursions resistance. Continuous monitoring (CGM) offers real-time insights to tailor dietary interventions, improving outcomes reducing complications. Despite advancements, gaps persist in understanding nutrient–drug interactions, particularly emerging antidiabetic agents. underscores need for integrating carbohydrate-focused strategies pharmacotherapy management. Future research should prioritize trials leveraging CGM technology explore how index, load, quality interact newer medications. Such studies can refine evidence-based recommendations, support individualized care plans, improve long-term outcomes. Addressing systemic barriers, such as limited access dietitians underserved regions, is critical equitable care. Expanding roles of community health workers training healthcare providers basic nutrition counseling bridge gaps, promoting sustainable inclusive management strategies. These efforts are essential advancing personalized, effective, individuals diabetes.

Language: Английский

---

Therapeutic Potential of Sodium–Glucose Cotransporter-2 Inhibitors in Nonalcoholic Fatty Liver Disease: A Network Meta-analysis

American Journal of Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

1Department of Pharmacology and Therapeutics, College Medicine Medical Sciences, Arabian Gulf University, Manama, Kingdom Bahrain; 2Dental Post Graduate Training Department, PHCC, Bahrain. The authors have no conflicts interest to declare. Supplemental digital content is available for this article. Direct URL citations appear in the printed text are provided HTML PDF versions article on journal's Web site (www.americantherapeutics.com). This study pooled data from studies that public domain.

Language: Английский

---

Update on the Efficacy and Safety of Sodium–Glucose Co-Transporter 2 Inhibitors in Patients with Chronic Diseases: A Systematic Review and Meta-Analysis

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 202 - 202

Published: Jan. 23, 2025

Background: Sodium–glucose co-transporter-2 (SGLT2) inhibitors have emerged as vital medications for the management of type 2 diabetes mellitus (T2DM). Numerous studies highlighted cardioprotective and renal protective benefits SGLT2 inhibitors. Consequently, it is essential to assess their efficacy safety in patients with chronic diseases. Method: We conducted a systematic review meta-analysis randomized controlled trials (RCTs) evaluating effects on major cardiovascular outcomes T2DM, heart failure (HF), kidney disease (CKD). searched PubMed, Cochrane, Embase databases published between 30 September 2021 17 May 2023. The primary interest included nonfatal myocardial infarction (MI), hospitalization (HHF), death, stroke. assessed were hypoglycemia, urinary tract infections (UTIs), acute injury (AKI). Result: identified 13 RCTs involving 90,413 participants. In significantly reduced risk MI by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [CI]: 0.78–0.98), HHF 33% (HR 0.67, CI: 0.62–0.74), cardiac death 15% 0.95, 0.80–1.13). However, they did not reduce stroke 0.85, 0.75–0.95). HF, 28% 0.72, 0.66–0.77) 0.80–0.96). For CKD, 35% 0.65, 0.55–0.76) 16% 0.84, 0.73–0.96). Regarding outcomes, increase hypoglycemia or nor (UTIs) HF (AKI) HF. UTIs 8% (risk [RR] 1.08, 1.01–1.16) T2DM AKI 22% (RR 0.78, 0.67–0.89) 19% 0.81, 0.69–0.97) respectively. Conclusions: demonstrated significant improvement CKD while also maintaining favorable profile. These findings advocate broader application diseases, particularly reducing incidence MI, HHF, death. Further research optimize use across diverse patient populations stages disease.

Language: Английский

---

Computational Drug Repositioning in Cardiorenal Disease: Opportunities, Challenges, and Approaches

PROTEOMICS, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

There is currently increased interest in drug repositioning programs, namely the identification of new therapeutic areas for already approved drugs, both academia as well biotech and pharmaceutical industry. Since 2012, number publications indexed MEDLINE on or repurposing exponentially increasing with a peak year 2021 due to worldwide search options combat COVID-19 pandemic [1]. Drug repositioning, however, not new, companies have ever since been looking additional market opportunities their products, particular when patents expire generics manufacturers enter initial approvals [2, 3]. In pharma world, term indication expansion also often used instead repurposing. patients suffering from rare disease who are lacking any therapies, represents very interesting efficient way bringing treatment patient fast [4]. This has stressed recent position paper International Rare Disease Research Consortium [5]. Several international consortia recognized trend toward Two US-based endeavors focusing Repurposing Hub EveryCure. Researchers Broad Institute created aim construct curate library FDA drugs that can be systematic screenings [6]. EveryCure's mission identify novel diseases via computational repositioning. European initiatives context Repo4EU (https://repo4.eu/) REMEDi4ALL (https://remedi4all.org/) consortia, being public–private partnerships develop tools but apply these selected indications. Next effort COVID-19, there at least three reasons why programs gaining momentum. First, molecular characterization processes continuously improving, we understand more about key pathways disease-modifying proteins, forming basis find counterbalancing dysregulations level. Second, arsenal tools, methods, workflows getting better matching pathobiology mechanism action (MoA), identifying connections thus potential targets intervention. And third, list successful cases longer. Even current blockbuster GLP1 agonists seen positive examples, scientifically commercially. Initially developed diabetes mellitus, this compound class meantime obesity clinical development several indications across different areas. viewpoint article, will discuss (i) experimental approaches discover opportunities, (ii) challenges further discovered compounds, (iii) kidney cardiovascular (CVD). observation-driven trials practice methods such binding assays phenotype screens, systematically opportunities. These make use information direct targets, affected biological mechanisms, side effects, omics signatures action, data electronic health records (EHRs) registries [7-10]. Key given Figure 1 discussed following sections. A major challenge one most crucial early steps discovery selection an appropriate target. For majority target known, always responsible drug's full efficacy potential. Information nevertheless target-based by which causally linked and/or progression [11]. Databases holding drug-target relations include, example, DrugBank [12], Therapeutic Target Database [13], STITCH EMBL-EBI [14]. open-source aiming consolidate sources associate Open Targets platform [15] Pharos [16]. comprehensive integrates types genetic associations, gene expression data, pathway information, results literature-mining prioritize human diseases. The driven researchers collaboration between scientific institutions companies. Users option either evaluating individual proteins (potential targets) searching (phenotype) [15]. web application consolidating established "Illuminating Druggable Genome" consortium Like Targets, users (protein) presented lists ranked respectively. Protein furthermore classified into four categories, Tclin (targets, drug), Tchem activity cutoff <30 nM), Tbio high annotation score based literature antibodies targeting protein), Tdark (targets without known compounds low scores literature). Especially category prime candidates approaches. Si et al. recently identified set promising chronic analysis proteomics transcriptomics combination Mendelian randomization investigation protein–protein interactions colocalization protein-coding genes [17]. might pave beneficially impact course disease. Fu similar approach evaluate relevance medications osteoarthritis [18]. They propose thiazolidinediones agents predicted role PPARG progression. protein structure-based Structure-based cheminformatics than bioinformatics-driven leverage structural similarities same drugs. Known pharmacokinetic profiles safety approach. broadly traditional advanced AI/ML-aided high-quality structures receptor ligands. Traditional high-throughput vitro, whereas machine learning algorithms process facilitates docking simulations, accuracy efficiency [19]. core strategy contrast only focus single compare whole (i.e., patterns abundance changes) various those reverse signature [20]. landmark study was published 2006 Lamb making 164 transcriptome level, dataset they called Connectivity Map [21]. meantime, extended thousands signature-based "connectivity mapping". To generate total over million profiles, focused 1000 encode 80% variation transcriptional creating L1000 [22]. integrated other resources within Library Integrated Network-based Cellular Signatures (LINCS) program, including proteomic, metabolomic, epigenomic [23]. publicly available accessible iLINCS web-based [24]. applications Mergeomics 2.0 R package integrating multi-omics reveal insights pathways, networks, drivers important pathogenesis ultimately predict [25]. functional module PharmOmics matches multi-omics-informed networks [26]. designed enable summary statistics multiomics sets, networks. PharmGWAS database leverages genome-wide association studies (GWAS) candidate repurposing, resistance, (iv) effects broad range GWAS datasets retrieved biobanks consortiums, deposited compound-perturbed CMap2.0 SigCom LINCS [27]. Single-cell Guided Pipeline Aid Drugs (ASGARD) uses scRNA-Seq samples attempts highest respective [28]. aims model complex systems level analyze among entities, diseases, By mapping onto network, measurements connectivity, proximity, cluster formation interactions, regulatory allow predictions silico Guala Sonnhammer tested network crosstalk-based constructed benchmark performance assessment network-based [29]. cross-talk sets disease-related genes, calculated distinct measures. evaluated shortest path every its closest [30], separate estimate crosstalk links two nodes [31-33]. Sadegh proposed (NeDRex) gene, protein, drug, target, annotations relationships [34]. NeDRex incorporates state-of-the-art case exemplified applicability extracting meaningful ovarian cancer starting seed nodes. obtained contained newly connector which, together participate relevant could using alone. Maier Drugst.one provides user-friendly, utilities interactive visualization capabilities [35]. 14 covering protein/gene, tool enrich proteins/genes clinically associations. Other include integration display adjacent project network. Yang DRONet framework effectiveness comparative combining embeddings, generated heterogeneous drug-disease ranking specific utilizing like RankNet, LambdaRank, LambdaMART [36]. Advances DNA/RNA sequencing enabled models derived mapped interactome Cheng Genome-wide Positioning Systems whole-exome approximately 5000 15 taken Cancer Genome Atlas, prioritizing [37]. Validation showed ouabain, cardiac arrhythmia heart failure, exhibited significant antitumor lung adenocarcinoma pathways. Moreover, another group proximity hundreds drug–disease associations [38]. validated against large-scale supported mechanistic vitro demonstrating risk coronary artery carbamazepine decreased hydroxychloroquine, compared levetiracetam. highlights interactome-based uncovering existing understanding broader Fiscon stated footprints randomly scattered colocalized highly interconnected subnetworks [39]. effective off-target adverse should proximal module. frameworks five metrics, breast prostate neoplasms, schizophrenia, liver cirrhosis. Ruiz introduced multiscale interactome, method disease-perturbed functions [40]. Their comprised 17,660 9798 functions, 1661 840 performing random walks evaluates propagation indirect enabling prediction treatments, related alter treatments reactions. comparing diffusion research groups atopic dermatitis [41], [42], non-alcoholic fatty [43], metabolic syndrome [44], cardiorenal later section examples rather just leveraging drug-specific dysregulations. REpurposing BIOlogical Pathways (DREBIOP) exemplary concepts comprehensively utilizes where effect mediated through [45]. authors exemplify beneficial ergocalciferol rickets interference vitamin D pathway. Another example pathway-based subtypes driver overcome resistance [46]. Knowledge-based enhance incorporating domain-specific knowledge graph-based structures, tasks providing deeper interactions. Graph embeddings advance multi-modal nodes, relationships, entire sub-graphs low-dimensional vectors. Himmelstein modeled graph 11 entities 24 relationship types, 29 public cover anatomies, pharmacologic classes, symptoms, entity [47]. paths correlating compound–disease pairs previously shown effective. Additionally, were DrugCentral trial data. eight epilepsy. Jain address issue insufficient specificity work [48]. Diluted coarse clustering limit ability synergies. Therefore, create hypergraphs, hyperedges this, converted modification node2vec algorithm. KG. Seven Alzheimer's Ghorbanali homogeneous features along negative unified latent space [49]. unknown sub-graph. Prediction area under curve ∼90% achieved. coronavirus infection skin-related predicted, conditions having demonstrated studies. Santos provide infrastructure facilitate automatic analysis, visualization, extraction [50]. 26 biomedical databases, literature. It built precision medicine decision-making. Machine graph. Its significantly higher CT45 serous adenocarcinoma, confirming biomarker long-term survival. Amiri Souri DT2Vec+ link [51]. shows predicting degree type proposing cancer-specific biomarkers. Lobentanzer unify fragmented landscape simplify task-specific KGs [52]. Biocypher offers focuses modularity, reproducibility, harmonization, reusability, accessibility. builds top rigid standards allows exchanges, modifications, extensions ontologies map concepts. Multiple act proof concept demonstrate practical use, federated Care-for-Rare project, multiple children's hospitals collaborate train shared while keeping decentralized private locally employed, sharing model's configuration parameters anonymous results. active hold combined ML unravel reported As articles almost tripled last decade continues grow 850,000 abstracts annually, increasingly relies automated text mining natural language processing methods. Deep technologies long short-term memory, convolutional neural bidirectional encoder representations transformers [53]. Challenges abbreviations ambiguity terms, symbols identical common phrases unspecific sub-strings falsely part longer, entries. contrast, rule-based definition stringent domain experts. Although involves manual curation longer cycles, it overall certain [54]. extract ideally causal genes/proteins, form intermediate genes/proteins. commonly resource storing genes/proteins DisGeNet [55]. Similarities Kumar epilepsy paroxetine seizures [56]. Data extracted SIDER [57], however seems no maintained update dates back 2015. events event reporting system still regularly updated. Paci measure reposition CVDs [58, 59]. formulated side-effect distal effects. vast amounts real-world captured EHRs, demographics, diagnoses, outcomes, lab results, explore correlations outcomes originally [60]. Retrospective analyses EHR hand lead de-novo validate findings Metformin, primarily therapy diabetes, found reduce dementia 2 after statistical databases [61]. Deep-learning emulate retrospective large Liu [62]. UK Biobank valuable around half participants deidentified [https://www.ukbiobank.ac.uk/]. 10 years. attractive addressing questions beyond exploration events, comorbidities groups. Main screenings. screen wide manner. High-throughput target-binding screening rely cellular animal prior targets. interact potentially modulate [63]. Phenotype usually performed cell-based determining readouts cell viability, apoptosis, motility, morphology, monitor signaling Asawa al., 8000 viability polycystic cells anti-proliferative [64]. Observations considered serendipitous play field led past [65]. prominent sildenafil initially systemic hypertension erectile dysfunction observed "side effects" [66], minoxidil treat inducing hair regrowth alopecia areata [67], amantadine influenza now symptoms Parkinson's [68]. Most until findings. Accessible Biobank, datasets, paved data-driven too determine biology-driven probability success viable eventually mix complementary applied increase chances success. holds references conducted renal No matter discovered, first step clinic next chapter. Repositioning described shortcut time drastically decrease costs. Widely figures report takes 10000 start end up average 10–17 years comes mean price tag 1.6 2.8 billion USD [69, 70]. exact savings achieved time, risk, money unclear, some conflicting evidence. Some reviews suggest 30% efforts product marketing, 10% (NDAs) general, argue repurposed do necessarily rates limiting factor [71]. Once utilization marketing remains cost-intensive challenge, referred "valley death" basic [72]. Numerous experts state benefit lies availability profile preclinical test even (safety) may skipped Phase II III. criteria, straightforward obvious, as: safe studies, does adequately rec

Language: Английский

---

Sodium-glucose co-transporter 2 inhibitors: a pleiotropic drug in humans with promising results in cats

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 28, 2025

Diabetes mellitus is a common metabolic disease in humans and cats. Cats share several features of human type-2 diabetes can be considered an animal model for this disease. In the last decade, sodium-glucose transporter 2 inhibitors (SGLT2i) have been used successfully as class hypoglycemic drug that inhibits reabsorption glucose from renal proximal tubules, consequently managing hyperglycemia through glycosuria. Furthermore, SGLT2i shown to cardiac, renal, other protective effects diabetic acting pleiotropic drug. Currently, at least six are approved by Food Drug Administration (FDA) use with diabetes, recently, two drugs were This narrative review focuses on treat We summarize data support controlling protecting against cardiovascular damage. also available literature regarding benefits these well Adverse related discussed.

Language: Английский

---

Sodium-glucose co-transporter inhibitors for APOL1 kidney disease: A call for studies

International Urology and Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

---