Drugs最新文献

{"title":"Glucose-Lowering Therapies in Type 2 Diabetes-Associated Sarcopenia: Mechanisms, Clinical Evidence and a Muscle-Centred Framework.","authors":"Jing Zhang, Xiaodan Zhai, Sha Sha, Le Zhang","doi":"10.1007/s40265-026-02408-9","DOIUrl":"https://doi.org/10.1007/s40265-026-02408-9","url":null,"abstract":"<p><p>Sarcopenia is increasingly recognised as a clinically important comorbidity in diabetes mellitus, particularly in older adults and individuals with long-standing type 2 diabetes. Because skeletal muscle is the principal site of insulin-stimulated glucose disposal, declines in muscle mass, quality, strength and physical performance may exacerbate insulin resistance and glycaemic instability and increase the risks of frailty, disability, falls, fractures, cardiovascular events and mortality. Contemporary glucose-lowering therapies have transformed diabetes care through established cardiorenal benefits and weight reduction, yet skeletal muscle outcomes are rarely prespecified or systematically assessed in pivotal trials. This evidence gap is especially relevant for weight-reducing agents such as glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, which are often associated with reductions in dual-energy X-ray absorptiometry-derived or bioelectrical impedance analysis-derived lean-mass estimates. However, these changes should be interpreted cautiously, as they often occur in the context of overall weight loss and may be influenced by alterations in body water. In addition, dual-energy X-ray absorptiometry- or dual-energy X-ray absorptiometry-derived lean-mass estimates do not directly quantify contractile skeletal muscle. Accordingly, reductions in lean-mass estimates alone are insufficient to infer clinically meaningful muscle loss without concurrent assessment of muscle strength or physical performance. This narrative review summarises the bidirectional mechanisms linking diabetes and sarcopenia and appraises major glucose-lowering drug classes from a muscle-centred perspective. It integrates mechanistic insights with human evidence on muscle-relevant outcomes, including body composition, strength and physical performance, and addresses practical safety and monitoring considerations in sarcopenia-prone phenotypes, including sarcopenic obesity. We also propose a pragmatic, hypothesis-generating Cardiorenal-Muscle Quadrant Framework that considers glycaemic efficacy and cardiorenal benefit alongside muscle reserve, functional status and treatment-related risks, with emphasis on functional monitoring, resistance exercise, nutritional optimisation and individualised glycaemic targets in older or frail adults.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rocbrutinib: First Approval.","authors":"Simon Fung","doi":"10.1007/s40265-026-02393-z","DOIUrl":"https://doi.org/10.1007/s40265-026-02393-z","url":null,"abstract":"<p><p>Rocbrutinib (; LP-168) is a fourth generation Bruton's tyrosine kinase (BTK) inhibitor with both covalent and non-covalent modes of binding, which allow it to inhibit both wildtype as well as mutant variants of BTK. It is being developed by Lupeng Pharmaceuticals primarily as a treatment for patients with B-cell malignancies. Rocbrutinib received its first approval in June 2026 in China for use in adult patients with mantle cell lymphoma (MCL) that is relapsed or refractory to BTK inhibitors, and who have received ≥ 2 systemic therapies (including BTK inhibitors). This article summarizes the milestones in the development of rocbrutinib leading to its first approval in this indication.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Lowers Fasting Hyperglycemia by Increasing Glucose Clearance in People with Moderately Controlled Type 2 Diabetes.","authors":"Sabine Kahl, Traci E LaMoia, Marc Jonuscheit, Geronimo Heilmann, Sophie Rohrer, Pavel Bobrov, Bedair Dewidar, Kalliopi Pafili, Theresia Sarabhai, Vera Schrauwen-Hinderling, Gerald I Shulman, Kitt Falk Petersen, Michael Roden","doi":"10.1007/s40265-026-02370-6","DOIUrl":"https://doi.org/10.1007/s40265-026-02370-6","url":null,"abstract":"<p><strong>Background/objective: </strong>Metformin is the most frequently prescribed antidiabetic drug worldwide; however, the mechanism by which it lowers blood glucose remains incompletely understood. The objective of this study was to examine the effects of metformin on whole-body and specifically on hepatic glucose and energy metabolism in type 2 diabetes.</p><p><strong>Methods: </strong>This open repeated-measures pilot study examined this question using Positional Isotopomer NMR Tracer Analysis (PINTA) to assess rates of endogenous glucose production (V_EGP), hepatic pyruvate carboxylase flux (V_PC), and citrate synthase (V_CS) flux in 16 men with moderately controlled type 2 diabetes (T2D; BMI 30 ± 3 kg/m², Hb_A1c 8.4 ± 1.4%) undergoing two examination days with (M+; 1 g twice daily) and without metformin (M-) treatment. Hepatic ATP and glycogen concentrations were quantified by ³¹P/¹³C magnetic resonance spectroscopy.</p><p><strong>Results: </strong>M+ reduced fasting glycemia by 18%, which could mostly be attributed to a 24% increase in rates of whole-body glucose clearance. Surprisingly, these changes were accompanied by a 58% increase in V_PC and a 34% increase in V_CS, due to a 26% increase in plasma glucagon concentrations. The increase in V_PC was offset by reductions in the contributions of glycerol conversion to glucose resulting in no change in V_EGP. Metformin decreased hepatic ATP content by 16% and increased plasma GDF-15 concentrations, but did not alter rates of net hepatic glycogenolysis.</p><p><strong>Conclusion: </strong>Metformin treatment in male individuals of European ancestry with moderately controlled T2D decreases blood glucose concentrations by increasing rates of whole-body glucose clearance. Metformin further inhibits glycerol-derived gluconeogenesis, which is consistent with complex IV, not complex I, being the molecular target of metformin action.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT04088851.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatigue in Inflammatory Bowel Disease: The Role of Drug Therapy Within a Holistic Management Framework.","authors":"Jai Sareen, Madelaine Prichodko, Lesley A Graff, Ali Keshavarzian, Robin M Voigt, Charles N Bernstein","doi":"10.1007/s40265-026-02397-9","DOIUrl":"https://doi.org/10.1007/s40265-026-02397-9","url":null,"abstract":"<p><p>Fatigue is one of the most common and disabling symptoms experienced by individuals with inflammatory bowel disease (IBD). Significant fatigue is experienced by approximately 40-80% of adults with IBD, with higher prevalence during active disease states but persisting in up to one-third of individuals who are in clinical remission. Fatigue is not solely a consequence of disease activity, but rather a unique and multifactorial manifestation of IBD. In this narrative review we synthesize evidence on the various mechanisms of fatigue in IBD, as well as pharmacological agents to address fatigue both directly or through secondary contributors including anaemia, psychiatric comorbidities, sleep disturbance, and pain. The review further situates pharmacological therapy within a holistic framework that integrates non-pharmacological approaches as part of a multidisciplinary approach to fatigue in IBD. Drug therapy has a meaningful role in this context, both when targeting disease-related inflammation and secondary contributors to fatigue. However, the evidence base for most of these approaches remains weak. It is clear that no single pharmacological agent will resolve IBD-related fatigue in isolation, but effective management should identify a patient's dominant contributors and address them systematically with both drug and nondrug intervention strategies. This framework should be delivered by a multidisciplinary team through an integrated care approach and optimally be guided by the patient's priorities and goals.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ciprocopan: First Approval.","authors":"Simon Fung","doi":"10.1007/s40265-026-02400-3","DOIUrl":"https://doi.org/10.1007/s40265-026-02400-3","url":null,"abstract":"<p><p>Ciprocopan (^®) is a small molecule inhibitor of complement factor B, which is a key component of the alternative complement pathway. It is being developed by Haisco Pharmaceutical Group for the treatment of complement-mediated disorders. In July 2026, ciprocopan received its first approval for treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have not previously received treatment with a complement inhibitor therapy in China. This article summarizes the milestones in the development of ciprocopan leading to this first approval.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibodies for the Prevention of Respiratory Syncytial Virus in Infants and Children: An Updated Systematic Review and Network Meta-analysis.","authors":"Jing Xiong, Chunyang Bai, Mingyao Sun, Janne Estill, Caixia An, Long Ge","doi":"10.1007/s40265-026-02395-x","DOIUrl":"https://doi.org/10.1007/s40265-026-02395-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Motivated by the emergence of a long-acting monoclonal antibody (clesrovimab), the availability of data from the complete MELODY trial cohort, and results from a large randomized trial (HARMONIE), we updated our prior network meta-analysis to evaluate the efficacy and safety of monoclonal antibodies for preventing severe respiratory syncytial virus (RSV) infection in infants.</p><p><strong>Methods: </strong>We searched for randomized controlled trials that examined the efficacy and safety of RSV infection prophylaxis with clesrovimab, motavizumab, nirsevimab, palivizumab, and suptavumab versus one another or placebo or no prophylaxis in infants. We performed a frequentist framework random-effects network meta-analysis and used the Grading of Recommendations, Assessments, Developments and Evaluation (GRADE) approach to assess the certainty of evidence.</p><p><strong>Results: </strong>Eighteen trials enrolling 33,283 infants were included. Clesrovimab (odds ratio [OR] 0.08, 95% confidence interval [CI] 0.02-0.37, moderate certainty), motavizumab (OR 0.12; 95% CI 0.07-0.19, moderate certainty), and nirsevimab (OR 0.20, 95% CI 0.11-0.34; moderate certainty) were associated with reductions in the rate of severe respiratory syncytial virus infection. Nirsevimab, motavizumab, clesrovimab, and intramuscular palivizumab were associated with reductions in RSV infection, and several agents were also associated with reduced hospitalization. Motavizumab and nirsevimab, and clesrovimab were associated with reductions in broader lower respiratory tract infection-related outcomes. Motavizumab reduced both mechanical ventilation use and intensive care unit admission. No significant differences were found in all-cause mortality and drug-related or serious adverse events.</p><p><strong>Conclusions: </strong>This updated network meta-analysis confirmed that the effectiveness and safety of clesrovimab were comparable to those of established monoclonal antibodies. Motavizumab, nirsevimab, and clesrovimab showed benefits for broader lower respiratory tract infection-related outcomes.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Veligrotug: First Approval.","authors":"Aisling McGuigan","doi":"10.1007/s40265-026-02390-2","DOIUrl":"https://doi.org/10.1007/s40265-026-02390-2","url":null,"abstract":"<p><p>Veligrotug (veligrotug-vvze; LUMVOA^™) is a monoclonal antibody insulin-like growth factor-1 receptor (IGF-1R) inhibitor that was developed by Viridian Therapeutics for the treatment of thyroid eye disease (also known as Graves ophthalmopathy/orbitopathy or thyroid-associated ophthalmopathy). In June 2026, veligrotug was approved by the US FDA for the treatment of thyroid eye disease regardless of disease activity or duration, based on positive results from two multinational phase III clinical trials. This article summarizes the milestones in the development of veligrotug leading to this first approval for thyroid eye disease.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal Nerve Injury and Regeneration: Mechanisms, Clinical Consequences, and Emerging Therapeutic Strategies.","authors":"Athar Shadmani, Anat Galor, Houri Esmaeilkhanian, Maja Kostic","doi":"10.1007/s40265-026-02396-w","DOIUrl":"https://doi.org/10.1007/s40265-026-02396-w","url":null,"abstract":"<p><p>The cornea is among the most densely innervated tissues in the body and depends on intact sensory and autonomic innervation to maintain epithelial integrity, tear film homeostasis, and ocular surface defense. Corneal nerve injury may occur after surgery, infection, inflammation, trauma, or systemic disease and can lead to reduced corneal sensitivity, impaired epithelial healing, dry eye, neuropathic pain, and neurotrophic keratopathy. Effective management requires both treatment of the underlying cause and restoration of a microenvironment permissive for reinnervation. This review examines the mechanisms underlying corneal nerve injury and repair, with emphasis on therapeutic strategies relevant to clinical translation. These include anti-inflammatory and immunomodulatory agents, growth factors and cytokines, blood-derived products, extracellular matrix-based therapies, stem cell- and secretome-based approaches, surgical neurotization, and physical stimulation modalities. We also highlight emerging challenges in the field, including the gap between structural nerve regeneration and functional recovery, limitations in clinical evidence, and barriers to therapeutic accessibility and implementation.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ruzinurad: First Approval.","authors":"Matt Shirley","doi":"10.1007/s40265-026-02399-7","DOIUrl":"https://doi.org/10.1007/s40265-026-02399-7","url":null,"abstract":"<p><p>Ruzinurad (^®) is an orally administered, small-molecule, selective inhibitor of urate transporter 1 (URAT1) that is being developed by the Jiangsu Hengrui Pharmaceuticals Co. for the treatment of hyperuricaemia associated with gout. By inhibiting the transport function of URAT1, ruzinurad suppresses uric acid reabsorption, thereby promoting uric acid excretion, leading to a reduction in serum uric acid levels. In May 2026, the National Medical Products Administration in China approved ruzinurad tablets for patients with hyperuricaemia associated with gout. This article summarises the milestones in the development of ruzinurad leading to this first approval for patients with hyperuricaemia associated with gout.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infections and the Opioid Epidemic: Changing Epidemiology and Treatment Options.","authors":"Laura C Fanucchi, Ellen Eaton, Nicholas Van Sickels, Michelle R Lofwall","doi":"10.1007/s40265-026-02364-4","DOIUrl":"https://doi.org/10.1007/s40265-026-02364-4","url":null,"abstract":"<p><p>The opioid epidemic has led to an infectious diseases syndemic, with injection drug use responsible for driving rising rates of HIV, viral hepatitis, and serious bacterial and fungal infections. Opioid use continues to cause devastating mortality, with over 80,000 opioid-involved overdose deaths in the USA in 2022. Despite the proven effectiveness of opioid agonist therapy, specifically methadone and buprenorphine, treatment coverage remains inadequate, with profound gaps in opioid use disorder (OUD) continuum of care. Injection-related infections, particularly skin and soft tissue infections, bacteremia, osteomyelitis, and infective endocarditis, have increased substantially since the early 2000s and carry a high risk of morbidity and mortality. Risk is further compounded by criminalization, stigma, incarceration, and comorbid psychiatric conditions. Emerging concerns such as xylazine-associated necrotic wounds illustrate the dynamic intersection of substance use and infectious disease. While direct-acting antivirals have made hepatitis C curable, barriers to treatment persist, and uptake of HIV prevention strategies, including pre-exposure prophylaxis, remains low among people who inject drugs. Integration of addiction treatment into infectious disease and hospital care improves outcomes, yet systemic and policy barriers limit access. Innovative models such as syringe service programs, mobile units, and inpatient addiction consult services demonstrate the feasibility of integrated, patient-centered care. Evidence gaps remain regarding optimal antibiotic strategies for serious infections in people with OUD, and research and policy must address exclusionary practices, stigma, and fragmented systems of care. A synergistic approach integrating OUD treatment, infectious disease management, risk reduction, and trauma-informed care is essential to reduce preventable deaths and improve long-term health outcomes.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}