Drug Design, Development and Therapy最新文献

{"title":"Vitamin D Alleviates Osteoarthritis Progression by Targeting Cartilage and Subchondral Bone via Myd88-TAK1-ERK Axis Suppression.","authors":"Xiang Gao, Yalin Min, Rui Lin, Dahong Liang, Min Zhang, Qixian Xiao, Yan Lu, Fucheng Zhang, Bilian Xu, Yanzhi Liu","doi":"10.2147/DDDT.S526064","DOIUrl":"10.2147/DDDT.S526064","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) causes irreversible joint damage, but current treatments fail to fully address its complex pathology. Emerging evidence suggests subchondral bone metabolic dysfunction may initiate OA. While vitamin D (VitD) is well-established for bone metabolism regulation in osteoporosis, its therapeutic potential in OA remains unclear despite observational studies suggesting protective effects. Our integrated in vivo/in vitro study demonstrates VitD's dual chondroprotective and osteogenic actions in OA.</p><p><strong>Methods: </strong>Sprague-Dawley rats (n=24) were divided into three groups: sham operation (Sham), OA model (OA), and OA+VitD treatment, with 8 rats in each group. Oral cholecalciferol (2.34 μg/kg/day) was administered for 6 weeks post-Monosodium iodoacetate (MIA) induction. The therapeutic potential of vitamin D was evaluated through a series of in vivo experiments. Human chondrocyte C28 cells were pretreated with TNFα (1ng/mL) to model inflammatory injury, followed by 1,25(OH)₂ D₃ (10^-2 μM) exposure for 72 hours to assess the VitD's effects of chondrogenesis and further investigate its underlying mechanism.</p><p><strong>Results: </strong>In OA rats, VitD suppressed femoral cartilage degradation (evidenced by 567.76% increased cartilage area, and 39.13% decreased Osteoarthritis Cartilage Histopathology (OACH) score and enhanced subchondral bone mass (61.81% higher BV/TV). At the molecular level, VitD downregulated the expression of cartilage matrix metalloproteinase 13 (MMP13), with a reduction of 74.72% compared to OA group. Additionally, VitD inhibit inflammatory signaling pathways, particularly through the MyD88-TAK1-ERK axis in chondrocytes, and decrease serum IL-6 level. Mechanistic validation of these findings was demonstrated by protein expression reduction of Myd88 (31.22%), phospho-ERK1/2 (66.11%), AP-1 (61.43%) and NFκB (34.36%) compared to OA group. In vitro, VitD also rescued ethanol-induced C28 cell viability loss while significantly upregulating cartilage anabolic markers.</p><p><strong>Conclusion: </strong>These findings establish VitD as a multimodal OA therapeutic agent targeting both cartilage catabolism and subchondral bone remodeling through Myd88-TAK1-ERK axis.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5855-5870"},"PeriodicalIF":4.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of a Cationic Polyurethane Carrier for Enhanced Topical DNA Delivery.","authors":"Florin Borcan, Adel Len, Titus Vlase, Gabriela Vlase, Zoltan I Dudas, Roxana Popescu, Ramona C Albulescu, Cristina A Dehelean, Camelia A Szuhanek","doi":"10.2147/DDDT.S510803","DOIUrl":"10.2147/DDDT.S510803","url":null,"abstract":"<p><strong>Background: </strong>Nucleic acids are increasingly being recognized for their potential as therapeutic agents for the treatment of a variety of pathologies, such as genetic diseases, viral infections, and cancer. However, the safe delivery of these negatively charged macromolecules to their intended sites of action remains a major challenge.</p><p><strong>Purpose: </strong>This study aimed to design and characterize cationic particles for use as nonviral vectors for nucleic acid delivery; another primary objective was to evaluate the biocompatibility between the particles and DNA.</p><p><strong>Methods: </strong>The particles were synthesized via a polyaddition process between isophorone diisocyanate and a mixture of polyethylene glycol and polycaprolactone diol. The structural characteristics were assayed using a variety of techniques, including measurements of pH, refractive index, and Zetasizer, drug release and penetration through an artificial membrane, SEM, FTIR and Raman spectroscopy, thermal analyses, cell viability, and in vivo evaluation of skin parameters.</p><p><strong>Results: </strong>The findings revealed that nearly neutral-pH particles were successfully synthesized, displaying a broad size distribution ranging from 400-900 nm, a prolonged release profile, and an encapsulation efficacy of 72.5%. Thermal analyses demonstrated that the samples remained stable at temperatures up to 200 °C, and the results of the spectroscopy, cell assay, and evaluations on mouse skin suggest that the obtained particles are safe for use as DNA carriers.</p><p><strong>Conclusion: </strong>Cationic polyurethane carriers present a potential alternative to the more established polyethylenimine. However, additional studies are necessary to fully assess the therapeutic effectiveness of these formulations.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5781-5799"},"PeriodicalIF":4.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bibliometric Study of Interleukin Cytokines in the Treatment of Intervertebral Disc Degeneration.","authors":"Haoran Wang, Xiaoqing Li, Sheng Wang, Jun Liu, Ning Xie","doi":"10.2147/DDDT.S523151","DOIUrl":"10.2147/DDDT.S523151","url":null,"abstract":"<p><strong>Background: </strong>In recent years, the research on the occurrence and development of interleukin in intervertebral disc degeneration has been more and more extensive. The purpose of this study is to predict the future research direction or prospect by analyzing the relevant literature in this field.</p><p><strong>Objective: </strong>Interleukin family cytokines are becoming more and more important in the research field of intervertebral disc degeneration, but all previous studies only focus on one aspect and are not comprehensive. We revealed the most influential countries and institutions in the field of interleukin, cytokine and intervertebral disc therapy. Systematic analysis of interleukin family cytokines and intervertebral disc degeneration and summary of related mechanisms will help to further promote the progress of related clinical treatment.</p><p><strong>Methods: </strong>The related articles published in 1 January 2015-1 December 2024 were all from network science (WOS), and charts were made and analyzed by using social science statistics software package and GraphPad Prism 8 software. Using VOS viewer software and CiteSpace software, the research trend of keywords is analyzed visually.</p><p><strong>Results: </strong>China has made the most significant contribution in this field. In addition, the research papers on IL-1 cytokines and intervertebral disc degeneration are the most, and Huazhong University of Science and Technology has published the most papers. Spine is the magazine that publishes the largest number of related documents. Preclinical medicine, especially immunology, plays a key role in this field. In hot spots, the focus of research can be divided into two parts (intervertebral disc degeneration and nucleus pulposus cells; The expression of interleukin and cytokine).</p><p><strong>Conclusion: </strong>This marks the first bibliometric analysis in this field and provides a comprehensive literature overview. Our findings clarify the future research direction and various cooperative relationships. Targeted therapy for interleukin and cytokine may be an important development trend in the future.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5801-5819"},"PeriodicalIF":4.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12248752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of <i>SiMiaoWan</i> in the Treatment of Hyperuricemia Based on Serum Metabolomics.","authors":"Mengping Guo, Bo Sun, Xiaochen Ding, Jingxiang Su, Xiuzhen Wang, Xiangjun Qiu","doi":"10.2147/DDDT.S533394","DOIUrl":"10.2147/DDDT.S533394","url":null,"abstract":"<p><strong>Background: </strong><i>SiMiaoWan</i> (SMW) can clear heat, expel dampness, tonify the kidney, strengthen the muscles, and treat damp heat in the spleen, stomach, and Lower Jiao. SMW is a formula commonly used for the clinical treatment of gout and hyperuricemia (HUA), especially asymptomatic HUA, and has shown remarkable therapeutic effects. This study aimed to investigate the therapeutic effect and mechanisms of SMW in a rat model of HUA using serum metabolomics.</p><p><strong>Methods: </strong>Rats were administered high levels of uric acid (UA) to establish a model of hyperuricemia and subsequently treated with SMW. Then, the levels of the biochemical indicators serum uric acid (SUA), alanine aminotransferase (ALT), aspartate transaminase (AST), urea nitrogen (BUN), and creatinine (CRE) were measured, and histological analysis of stained liver and kidney tissue sections was performed. Furthermore, blood samples were collected after the animal experiment for serum untargeted metabolomics analysis via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS) and subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis.</p><p><strong>Results: </strong>The levels of the biochemical indicators were significantly lower in rats treated with SMW than in control rats. Additionally, metabolomics and KEGG enrichment pathway analyses indicated that central carbon metabolism, protein digestion and absorption, and amino acid biosynthesis pathways may play important regulatory roles in the SMW-mediated lowering of the SUA level in hyperuricemic rats.</p><p><strong>Conclusion: </strong>SMW effectively reduced the SUA level in hyperuricemic rat models and alleviated the renal impairment induced by hyperuricemia. The mechanism of SMW is closely associated with pathways related to central carbon metabolism in cancer, protein digestion and absorption, and amino acid biosynthesis.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5761-5779"},"PeriodicalIF":4.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthraquinones from <i>Rheum officinale</i> Ameliorate Renal Fibrosis in Acute Kidney Injury and Chronic Kidney Disease.","authors":"Hao-Yu Feng, Yi-Qi Wang, Jianhua Yang, Hua Miao, Ying-Yong Zhao, Xiaojuan Li","doi":"10.2147/DDDT.S521265","DOIUrl":"10.2147/DDDT.S521265","url":null,"abstract":"<p><p>Renal diseases including acute kidney injury (AKI) and chronic kidney disease (CKD) has become a significant public health concern due to its high morbidity and mortality. <i>Rheum officinale</i> Baill (Polygonaceae) exhibits diuretic, renoprotective, lipid-lowering, anti-inflammatory, and antifibrotic properties. Accumulating evidence has highlighted the anthraquinones in <i>R. officinale</i> as key components contributing to its renoprotective effects. The available information on <i>R. officinale</i> was searched by several electronic database such as PubMed, Web of Science, Springer, ScienceDirect, etc. This review summarizes the anthraquinones and their renoprotective effects in <i>R. officinale</i>, evaluating its clinical potential for managing renal disease including AKI and CKD. Studies demonstrate that <i>R. officinale</i> contains bioactive components such as anthraquinones, stilbenes, phenylbutazones, and tannins. This review discusses the renoprotective effects of <i>R. officinale</i>, including improvements in renal function, reduction of podocyte damage, and inhibition of renal fibrosis. These effects are mediated through the regulation of pro-inflammatory (IκB/NF-κB and Keap1/Nrf2), pro-fibrotic (TGF-β1/Smad and Wnt/β-catenin), AMP-activated protein kinase and phosphoinositide 3-kinase signaling pathways in AKI and CKD. Additional mechanisms include modulation of anti-ageing Klotho expression, autophagy, and apoptosis. These findings expand the understanding of the therapeutic effects on AKI and CKD of <i>R. officinale</i> and provide valuable information on its clinical application in traditional Chinese medicine. This review presents a concept-driven therapeutic strategy for renal disease management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5739-5760"},"PeriodicalIF":4.7,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Toxicity of Dimethyl Sulfoxide Combined with the Alkylating Agent MNU on Mice: Focusing on Mortality and Activity Impairment.","authors":"Weiming Yan, Qiurui He, Lin Xiao, Yuxin Xia, Xiangrong Zheng, Xiaohong Zhang","doi":"10.2147/DDDT.S521506","DOIUrl":"10.2147/DDDT.S521506","url":null,"abstract":"<p><strong>Objective: </strong>Dimethyl sulfoxide (DMSO) is known to enhance the absorption of chemicals. This study investigated the effects of DMSO in combination with the alkylating agent, N-methyl-N-nitrosourea (MNU), on the activity and mortality of mice, providing foundational data for solvent mixture use and health impact assessment.</p><p><strong>Methods: </strong>Twelve male SPF C57BL/6J mice were divided into three groups (n=4): DMSO group (D), DMSO combined with low-dose (L), and high-dose MNU group (H). Mice in D received intraperitoneal injections of pure DMSO solution at 12 mL/kg. The L or D group was injected with a DMSO solution containing 40 mg/kg or 60 mg/kg MNU at 12 mL/kg, respectively. Mice were monitored for changes in body weight, activity levels (walking, body stretching, fur condition), and mortality at various time points.</p><p><strong>Results: </strong>Pre-injection, all groups showed no statistical differences in weight or DMSO dose, while the MNU injection dose was significantly different (H>L>D). Within 2 hours post-injection, all mice except one in the D group exhibited reduced mobility, hunched posture, and lethargy. Mortality progressed rapidly, with one D and two L mice dying by 12 hours, followed by additional deaths (one D, two L, and two H mice) at 24 hours. By 36 hours, all mice in L and H groups had died, while one D mouse recovered normal activity. At the 48-hour endpoint, only one D mouse survived with normal behavior. No significant differences in weight, activity levels and mortality changes were observed in surviving mice throughout the study period.</p><p><strong>Conclusion: </strong>DMSO has certain toxicity, and when combined with alkylating agents such as MNU, it can lead to reduced activity and an increased mortality rate in mice. It is recommended to closely monitor the mice during the use of such reagents and to establish appropriate research observation protocols.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5727-5737"},"PeriodicalIF":4.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significant Predictors of Azithromycin in Population Pharmacokinetic Analysis: A Systematic Review.","authors":"Runcong Zhang, Yuebin Fang, Yinhui Wang, Jing Fan, Weiming Yin, Weibin Fan, Yuetian Yu, Bin Lin","doi":"10.2147/DDDT.S519597","DOIUrl":"10.2147/DDDT.S519597","url":null,"abstract":"<p><p>Azithromycin is widely used to treat infections caused by susceptible bacteria and is the first-line treatment for mycoplasma pneumonia in pediatric patients. However, in clinical practice, large between-patient variability has been observed. Several population pharmacokinetic studies have been conducted to identify covariates and guide individualized therapy. This study evaluated published population pharmacokinetic studies and explored the significant covariates. The PubMed, Embase, and Web of science databases were systematically searched from their inception to 30 May 2024. Information on study design, characteristics, and final model parameters was extracted and compared. Time-concentration curves and forest plots were used to examine pharmacokinetic characteristics and identify covariates, respectively. Fifteen population pharmacokinetic studies were included in the review: three involved preterm neonates, two involved children, two involved pregnant/non-pregnant women, and eight involved adults. The median apparent clearance value was higher for adults (1.66 L/h/kg) than for children (1.28 L/h/kg) and preterm neonates (0.187 L/h/kg). For all populations, body weight significantly influenced the apparent clearance and distribution volume. In children, age and liver function influenced azithromycin clearance; whereas for women, clearance was reduced by 38% in case of pregnancy, non-African descent, and oral contraceptive use. Azithromycin was shown to distribute across plasma, tissues, and cells, with notable concentration differences. The azithromycin dose regimen is determined based on body weight. However, for children and women, additional predictors should be considered for individualized therapy. Further azithromycin population studies of the dose-exposure-response relationship are needed to achieve accurate dose adjustments.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5709-5725"},"PeriodicalIF":5.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Driven Innovations in Oncology Drug Discovery: Transforming Traditional Pipelines and Enhancing Drug Design.","authors":"Fatimah G Albani, Sahar S Alghamdi, Mohammed M Almutairi, Tariq Alqahtani","doi":"10.2147/DDDT.S509769","DOIUrl":"10.2147/DDDT.S509769","url":null,"abstract":"<p><p>The integration of artificial intelligence (AI) into oncology drug discovery is redefining the traditional pipeline by accelerating discovery, optimizing drug efficacy, and minimizing toxicity. AI has enabled groundbreaking advancements in molecular modeling, simulation techniques, and the identification of novel compounds, including anti-tumor and antibodies, while elucidating mechanisms of drug toxicity. Additionally, AI has emerged as a critical tool in precision medicine, driving the formulation and release of targeted therapies and improving the development of treatments for oncology and central nervous system diseases. Furthermore, AI-assisted clinical trial designs have further optimized the recruitment and stratification of patients, reducing the time and cost of trials. Despite these advancements, challenges such as data integration, transparency, and ethical considerations persist. By synthesizing current innovations, this manuscript provides a comprehensive analysis of AI-driven approaches in drug discovery and their potential to advance oncology therapeutics and precision medicine. It examines the transformative role of AI across the drug development continuum, with a focus on its applications in computer-aided drug design (CADD), generative artificial intelligence (GAI), and high-throughput screening (HTS).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5685-5707"},"PeriodicalIF":4.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ternary Solid Dispersions as an Alternative Approach to Enhance Pharmacological Activity.","authors":"Salma Amaliah, Diah Lia Aulifa, Amirah Mohd Gazzali, Arif Budiman","doi":"10.2147/DDDT.S533359","DOIUrl":"10.2147/DDDT.S533359","url":null,"abstract":"<p><p>Poor solubility and limited bioavailability remain significant challenges in developing oral drugs, affecting the clinical efficacy of many active pharmaceutical ingredients (APIs). Enhancing solubility has become a primary focus in improving API bioavailability. Among the most commonly employed strategies are amorphous solid dispersions (ASDs) and co-amorphous systems, collectively called binary systems. However, these systems often suffer from wettability and physicochemical limitations, which can hinder drug release. Adding a third component to form ternary solid dispersions (TSDs) significantly enhance drug release and bioavailability, ultimately improving therapeutic outcomes. While numerous studies have investigated the application of TSDs in enhancing API pharmacological activity, only limited studies have a comprehensive analysis of this approach. Therefore, this review aims to summarize and elucidate the mechanisms of TSD systems in improving pharmacological activity. The review includes available literature from Scopus, PubMed, and Google Scholar that utilizes the keywords \"ternary solid dispersion\" and \"pharmacological activity\", summarizing the importance of TSDs in therapeutic formulations for enhancing pharmacological activity. Various in vitro and in vivo studies consistently demonstrate that TSDs outperform binary systems by significantly enhancing the pharmacological effects of diverse therapeutic agents, including those with antioxidant, anti-inflammatory, anticancer, antibacterial, anticholinesterase, antihyperlipidemic, anti-hypoglycemic, anti-Alzheimer's, antidiabetic, and hepatoprotective properties. This approach holds significant promise as an alternative for the formulation of low-solubility pharmaceuticals.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5663-5684"},"PeriodicalIF":4.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide Therapy and Accelerated Sarcopenia in Older Adults with Type 2 Diabetes: A 24-Month Retrospective Cohort Study.","authors":"Qingjuan Ren, Lei Zhi, Hongfang Liu","doi":"10.2147/DDDT.S531778","DOIUrl":"10.2147/DDDT.S531778","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate changes in muscle mass and strength among older adults with type 2 diabetes who were treated with Semaglutide.</p><p><strong>Methods: </strong>This was a retrospective cohort study comparing elderly patients with type 2 diabetes receiving Semaglutide to a matched control group. Changes in muscle mass and function over 24 months were assessed. Muscle mass was measured using the appendicular skeletal muscle mass index (ASMI), while muscle function was evaluated through grip strength and gait speed measurements. Differences between the two groups and changes before and after treatment were analyzed using the <i>t</i>-test. Additionally, multivariable linear regression models were constructed to identify clinical predictors of accelerated muscle loss during Semaglutide treatment.</p><p><strong>Results: </strong>The study involved 220 patients treated with Semaglutide and 212 control subjects. The prevalence of sarcopenia among participants was 27.7%. Semaglutide treatment significantly reduced both body mass index and muscle mass compared to controls. Notably, divergent patterns emerged in functional measures. Grip strength initially improved but then declined in men, while it continued to decrease in women. Gait speed significantly reduced in both genders. Multivariable analysis identified Semaglutide dosage, baseline ASMI, and gait speed as independent predictors of muscle loss.</p><p><strong>Conclusion: </strong>The use of Semaglutide is associated with muscle loss and functional decline in older adults with type 2 diabetes, particularly at higher doses. This effect is especially significant in patients with sarcopenia. Consequently, it is crucial to assess the risks and benefits for each elderly patient individually and to implement appropriate monitoring and interventions. The potential for nutritional supplementation and targeted exercise regimens to counteract semaglutide-associated muscle decline merits systematic investigation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5645-5652"},"PeriodicalIF":4.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}