Drug Design, Development and Therapy最新文献

{"title":"Novel Hybrid Scaffold of Pyrazole, Thiazole, and [1,2,3]triazole: Eco-Friendly Synthesis by DABCO, Anti-HIV-1 RT, and In Silico Studies.","authors":"Muneera S M Al-Saleem, Ahmed A Elhenawy, Ohoud F Al Sharif, Sayed M Riyadh, Magdi E A Zaki, Sobhi M Gomha","doi":"10.2147/DDDT.S627223","DOIUrl":"https://doi.org/10.2147/DDDT.S627223","url":null,"abstract":"<p><strong>Background: </strong>The emergence of drug-resistant HIV-1 strains and limitations of current reverse transcriptase (RT) inhibitors support the development of structurally novel antiviral scaffolds. Hybrid azole systems may provide complementary interactions within the HIV-1 RT binding pocket.Purpose: To synthesize novel pyrazole-thiazole-[1,2,3]triazole hybrids using an eco-friendly DABCO-mediated approach and evaluate their anti-HIV-1 RT activity and structure-activity relationships using experimental and computational methods.</p><p><strong>Methods: </strong>Fourteen hybrid compounds were synthesized from hydrazone-1-carbothioamide 3 through cyclo-condensation with hydrazonoyl chlorides 4a-j or 5a-d using DABCO, affording arylazo-thiazoles 6a-j and hydrazono-thiazol-4(5H)-ones 7a-d. Structures were characterized by IR, 1H-NMR, 13C-NMR, and mass spectrometry. Molecular docking against HIV-1 RT (PDB: 3V81) was used to prioritize candidates, and six compounds were evaluated using an ELISA-based RT inhibition assay with zidovudine as reference. DFT, molecular electrostatic potential, and intramolecular charge-transfer analyses were also performed.</p><p><strong>Results: </strong>The target compounds were obtained in 90-95% yields. The six tested derivatives showed IC50 values of 0.192-1.693 μg/mL. Compound 7a was the most active (IC50 = 0.192 ± 0.008 μg/mL), with activity comparable to zidovudine (0.201 ± 0.009 μg/mL; p = 0.74), and showed the most favorable docking energy (-6.37 kcal/mol) with a key Lys65 hydrogen bond. The hydrazono-thiazolone series 7 generally outperformed series 6. DFT analysis associated higher hardness and wider HOMO-LUMO gaps with improved activity.</p><p><strong>Conclusion: </strong>Compound 7a represents a promising HIV-1 RT inhibitor lead, supported by consistent enzymatic, docking, and electronic-structure findings. Further cytotoxicity and cell-based antiviral studies are required to establish its selectivity and preclinical potential.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"627223"},"PeriodicalIF":6.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105627","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":"Antibody-Drug Conjugates in Breast Cancer: Therapeutic-Window Engineering, Tumor Heterogeneity, and Immunotherapy Combinations.","authors":"Shiyan Zeng, Li Wang, Wanqin Zeng, Lei Sun","doi":"10.2147/DDDT.S638805","DOIUrl":"https://doi.org/10.2147/DDDT.S638805","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have become a major therapeutic class in breast cancer, but their clinical performance cannot be predicted by antigen expression alone. This review uses therapeutic-window engineering as a unifying framework to connect ADC molecular architecture with tumor heterogeneity, clinical positioning, resistance, immune effects, and toxicity. We examine how target selection, antibody properties, linker stability, payload mechanism and membrane permeability, drug-to-antibody ratio (DAR), conjugation homogeneity, and intratumoral delivery jointly determine efficacy and safety. We then distinguish established clinical uses from investigational strategies across HER2-positive, HER2-low/ultralow, hormone receptor-positive/HER2-negative, and triple-negative breast cancer, reflecting the rapid movement of ADCs into earlier treatment lines and selected early-stage settings. Rather than treating ADCs as a homogeneous class, we critically assess how payload class, linker behavior, bystander killing, Fc-mediated activity, and baseline immune context may favor or limit combinations with immune checkpoint inhibitors. We also map resistance along the delivery-to-kill cascade and integrate practical safety considerations, including interstitial lung disease/pneumonitis, hematologic toxicity, ocular events, and overlapping toxicities in combination regimens. Three principles emerge: ADC efficacy is a systems property; strategies that broaden tumor coverage may also increase normal-tissue exposure; and successful combinations require platform-specific rather than class-wide rationale. Future progress will depend on biomarker-guided sequencing, rational platform selection, and safety-adapted optimization of the therapeutic window.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"638805"},"PeriodicalIF":6.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105611","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":"GLP-1 Receptor Agonists Versus DPP-4 Inhibitors and Incident Dementia Risk in COVID-19 Survivors with Type 2 Diabetes: A Target Trial Emulation Study.","authors":"Kuo-Chuan Hung, Ting-Sian Yu, Ping-Hsin Liu, Yi-Chen Lai, I-Wen Chen","doi":"10.2147/DDDT.S638249","DOIUrl":"https://doi.org/10.2147/DDDT.S638249","url":null,"abstract":"<p><strong>Purpose: </strong>Type 2 diabetes mellitus (T2DM) and COVID-19 are independently associated with an elevated risk of dementia, and COVID-19 survivors with T2DM may represent a clinically vulnerable population in whom metabolic, inflammatory, and vascular factors coexist. However, whether antidiabetic treatment choice is associated with incident dementia risk in this population remains unknown.</p><p><strong>Methods: </strong>In this target trial emulation using the TriNetX US Collaborative Network, we compared COVID-19 survivors aged ≥50 years with T2DM initiating glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy with those initiating dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy between January 1, 2020 and December 31, 2024. We applied an active-comparator, new-user design with a 90-day survivor landmark and 1:1 propensity score matching. The primary outcome was incident all-cause dementia (a composite of vascular dementia, Alzheimer's disease, and other dementias). Secondary outcomes included dementia subtypes, mild cognitive impairment, glycemic outcomes, and all-cause mortality.</p><p><strong>Results: </strong>After matching, 25,263 patients per group were followed for up to 6 years (median, 919 days [GLP-1RA] vs 955 days [DPP-4i]). GLP-1RA initiation was associated with a lower hazard of incident dementia (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.58-0.72), vascular dementia (HR, 0.67; 95% CI, 0.52-0.85), and Alzheimer's disease (HR, 0.74; 95% CI, 0.59-0.93), as well as more favorable glycemic control and lower all-cause mortality (HR, 0.63; 95% CI, 0.59-0.68). The estimate for mild cognitive impairment was borderline (HR, 0.87; 95% CI, 0.75-1.00) and not consistently supported across sensitivity analyses. The association with incident dementia remained evident after the 6-month landmark analysis (HR, 0.66; 95% CI, 0.58-0.75) and was consistent across sensitivity and subgroup analyses.</p><p><strong>Conclusion: </strong>Among COVID-19 survivors with T2DM, GLP-1RA initiation was associated with a lower hazard of incident dementia than DPP-4i initiation. These hypothesis-generating results warrant confirmation before they can be used to inform clinical decision-making.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"638249"},"PeriodicalIF":6.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105593","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":"Tegileridine versus Sufentanil for Patient-Controlled Intravenous Analgesia After Cesarean Delivery: A Randomized Double-Blind Trial.","authors":"Jing Hu, Lianchun Ou, Fangyun Wei, Yanmin Wei, Xinying Guo, Yong Zhang, Haiping Xu, Lingyu Wang","doi":"10.2147/DDDT.S638340","DOIUrl":"https://doi.org/10.2147/DDDT.S638340","url":null,"abstract":"<p><strong>Background: </strong>Postoperative nausea and vomiting (PONV) remains one of the most common opioid-related adverse events after cesarean delivery despite multimodal analgesia. Tegileridine, a biased μ-opioid receptor agonist, may offer effective analgesia with fewer opioid-related adverse events. This randomized, double-blind trial compared tegileridine versus sufentanil for patient-controlled intravenous analgesia (PCIA) after cesarean delivery.</p><p><strong>Methods: </strong>Chinese Clinical Trial Registry number: ChiCTR2600123056. Ninety-four parturients scheduled for elective cesarean were randomized to receive PCIA with tegileridine 5 mg or sufentanil 100 μg. The primary outcome was the 48-hour incidence of PONV. Secondary outcomes included other opioid-related adverse events (ORAEs), pain scores, PCIA bolus counts, rescue analgesia, Quality of Recovery 15 (QoR-15) scores, ambulation time, and hospital stay.</p><p><strong>Results: </strong>Ninety-two participants completed the study. Compared with the sufentanil group, the tegileridine group had a lower incidence of PONV (6.5% vs 23.9%; RR = 0.27 (95% CI: 0.08-0.91); OR = 0.22 (95% CI: 0.06-0.86); ARD = -17.4% (95% CI: -31.6 to -3.1%); P=0.039) and dizziness (6.5% vs 26.1%; P=0.022). Postoperative pain scores, PCIA bolus counts, rescue analgesic requirements, ambulation time, and hospital stay showed no statistically significant differences between groups. QoR-15 scores at 48 h were higher in the tegileridine group (median 125 vs 113; P<0.001).</p><p><strong>Conclusion: </strong>Among women undergoing cesarean delivery, tegileridine-based PCIA was associated with a lower incidence of PONV and dizziness and improved postoperative recovery quality compared with sufentanil, while postoperative analgesic outcomes were not significantly different between groups. These findings warrant confirmation in larger multicenter studies before routine clinical adoption.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"638340"},"PeriodicalIF":6.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105415","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":"Dexketoprofen Trometamol Plus Sufentanil for Analgesia After Thoracoscopic Radical Resection of Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial.","authors":"Ao Guo, Mengting Shen, Hanbin Wang, Jianliang Sun, Xinlei Lu","doi":"10.2147/DDDT.S634333","DOIUrl":"https://doi.org/10.2147/DDDT.S634333","url":null,"abstract":"<p><strong>Background: </strong>Evidence for adding dexketoprofen trometamol to sufentanil-based patient-controlled intravenous analgesia (PCIA) after thoracoscopic radical resection of lung cancer remains limited.</p><p><strong>Objective: </strong>To evaluate 48-hour opioid consumption, pain outcomes, and short-term adverse events with dexketoprofen trometamol plus sufentanil versus sufentanil-based PCIA alone.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled trial, 108 patients scheduled for thoracoscopic radical resection of lung cancer were randomized preoperatively (54 per group). After 18 post-randomization exclusions before PCIA initiation, 45 patients per group received the allocated intervention and were analyzed. All underwent unilateral uniportal anatomical segmentectomy with mediastinal lymph node dissection or sampling and received a standardized intercostal nerve block. Group S received sufentanil-based PCIA, and Group R additionally received dexketoprofen trometamol. The primary outcome was total 48-hour postoperative sufentanil consumption, including rescue doses.</p><p><strong>Results: </strong>Sufentanil consumption was lower in Group R than in Group S (78.03 ± 10.66 vs 96.78 ± 13.69 μg; reduction 18.75 μg, 95% CI 13.61 to 23.89; P<0.001), representing an approximately 19% reduction. Resting pain scores were lower at 12 and 24 hours (both P=0.004), meeting the revised Bonferroni threshold of P<0.005 for 10 time-point comparisons; the coughing-pain difference at 12 hours (P=0.006) did not meet this threshold. Resting-pain area under the curve was lower (P=0.009), but generalized estimating equations showed no significant overall group effect or group-by-time interaction for resting or coughing pain. Nausea occurred in 11.1% versus 28.9% (Pearson χ² P=0.035).</p><p><strong>Conclusion: </strong>Adding dexketoprofen trometamol reduced 48-hour sufentanil consumption in the analyzed population. Pain differences were time-specific secondary findings and did not establish sustained analgesic superiority. The nausea finding requires confirmation, and the trial was insufficient to establish safety for uncommon adverse events.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"634333"},"PeriodicalIF":6.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105577","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":"Mean Exposure Does Not Validate Target Attainment Predictions in Children [Response to Letter].","authors":"Juan Wu","doi":"10.2147/DDDT.S658319","DOIUrl":"https://doi.org/10.2147/DDDT.S658319","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"658319"},"PeriodicalIF":6.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105625","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":"Recent Advances in Cyclic Peptide-Based Therapeutic Strategies for Renal Cell Carcinoma: A Focused Review.","authors":"Liming Sun, Xiaoting Li, Yan Liu, Guangzhen Wu","doi":"10.2147/DDDT.S638461","DOIUrl":"https://doi.org/10.2147/DDDT.S638461","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), remains difficult to control after resistance to targeted therapy or immune checkpoint blockade develops. Cyclic peptides provide conformationally constrained and chemically adaptable scaffolds for direct target modulation, tumor-selective payload delivery, radiotheranostics, supramolecular assembly, and induced-proximity pharmacology. This focused mini-review groups cyclic peptide-based strategies according to the role played by the peptide in the therapeutic system. The peptide may act as the drug itself, carry a drug or radionuclide, guide a larger carrier, assemble into a drug-delivery material, or bring two proteins together. Direct RCC evidence is anchored by carbonic anhydrase IX (CAIX)-targeted DPI-4452/ZH2 radiotheranostics, cyclic Arg-Gly-Asp (cRGD)-guided small interfering RNA (siRNA) delivery to tumor endothelium, and PB1-p62-mediated polybromo 1 (PBRM1) degradation and immune sensitization. Drug-resistant non-RCC models are retained only as transferable design evidence for efflux-evasive or self-assembling delivery. We further discuss target heterogeneity, linker and assembly stability, pharmacokinetics, renal distribution, scalable synthesis, and the experimental controls required to attribute benefit to the cyclic peptide component. Although clinical therapeutic evidence remains limited, the emerging RCC-specific studies support a mechanism-matched development strategy for this drug class.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"638461"},"PeriodicalIF":6.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105232","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":"From Pharmacological Uncertainty to Inhalation Development: An Evidence-Gated Roadmap for <i>Codonopsis</i>-Derived Triterpenoid Saponins.","authors":"Xiaohua Zhang, Chunxia Yang, Ping Wang, Ping Yang, Shanru Liu, Shubin Liu, Xiaoling Yang","doi":"10.2147/DDDT.S647578","DOIUrl":"https://doi.org/10.2147/DDDT.S647578","url":null,"abstract":"<p><p><i>Codonopsis</i>-derived triterpenoid saponins merit investigation because preclinical studies identify immunomodulatory activity and a biologically active parent-metabolite relationship. Pulmonary delivery could increase exposure at a lung target while limiting unnecessary systemic exposure, but uncertain immune direction, membrane interactions, pulmonary absorption, and repeated-dose safety prevent a direct formulation recommendation. This critical narrative review evaluates chemical identity, lung pharmacology, and transferable delivery precedents using targeted searches updated through September 16, 2026 and a structured assessment of study relevance and limitations. Evidence is distinguished by material and route: defined saponins or fractions, composition-characterized botanical extracts, the associated metabolite echinocystic acid, and unrelated engineering precedents. Earlier anti-inflammatory lancemaside A studies and a 2026 immunostimulatory study in interferon-gamma-primed macrophages require matched replication rather than a claim of an established biphasic mechanism. Oral <i>C. lanceolata</i> extract efficacy in allergic lung inflammation and echinocystic acid pharmacology support further investigation but do not validate an inhaled parent saponin. No qualifying therapeutic aerosol-inhalation study of a <i>Codonopsis</i> saponin, standardized saponin fraction, or composition-characterized extract was identified in the searches performed. We propose four connected development stages: select a reproducibly beneficial active entity; establish pulmonary safety and local pharmacokinetics/pharmacodynamics with the simplest feasible formulation; correct a demonstrated delivery limitation when necessary; and integrate efficacy, device-patient suitability, storage stability, and manufacturing. Lipid carriers, spray-dried or spray-freeze-dried powders, mucus-modifying surfaces, and targeting systems are assessed against their measured benefits and failure modes. Numerical targets remain explicit development hypotheses rather than regulatory standards. The framework supports local pulmonary treatment as the initial objective and makes progression, reformulation, and termination conditional on evidence.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"647578"},"PeriodicalIF":6.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105536","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":"Median Effective Concentration of Ropivacaine for Ultrasound-Guided T₁₁ Thoracic Paravertebral Block in Patients with End-Stage Renal Disease: A Dixon Up-and-Down Dose-Finding Study.","authors":"Jinghui Ma, Jindi Cao, Xiangzhen Wang, Huanni Li, Wen Xu, Zejun Niu","doi":"10.2147/DDDT.S638060","DOIUrl":"https://doi.org/10.2147/DDDT.S638060","url":null,"abstract":"<p><strong>Background: </strong>Patients with end-stage renal disease (ESRD) may exhibit altered pharmacokinetic and pharmacodynamic responses to local anesthetics. But the ropivacaine concentration-response profile for ultrasound-guided T₁₁ thoracic paravertebral block (TPVB) in this population remains undefined. This study aimed to determine the median effective concentration (EC50) of ropivacaine for TPVB in ESRD patients undergoing peritoneal dialysis catheterization (PDC) and evaluate early postoperative recovery.</p><p><strong>Methods: </strong>In this prospective dose-finding study, patients aged 18-75 years with ESRD and ASA physical status II-III undergoing elective PDC received ultrasound-guided T₁₁ TPVB with 20 mL ropivacaine. Concentrations were assigned by the Dixon up-and-down method, starting at 0.50%: decrease by 0.05% after a successful analgesic or increased by 0.05% after a failed response. A successful response was defined as VAS ≤3 at skin incision without rescue analgesia; a failed response was defined as VAS >3 or rescue analgesia before or during incision. EC50 was estimated primarily by centered isotonic regression with the pool-adjacent-violators algorithm (CIR-PAVA), a nonparametric method suited to small Dixon samples; with probit regression, a parametric approach commonly used in prior EC50 studies, also performed for comparison. Recovery was assessed using the Quality of Recovery-40 (QoR-40) questionnaire at 24 hours postoperatively. This was a small single-arm exploratory study with no formal sample-size calculation, consistent with the sequential design.</p><p><strong>Results: </strong>27 patients completed the study. EC50 was 0.173% (95% CI: 0.100%-0.500%) by CIR-PAVA and 0.180% (95% CI: 0.109%-0.225%) by probit regression. The wider CIR-PAVA CI reflects the small sample size and limited precision. Median global QoR-40 score at 24 hours was 184.0. Five patients (18.5%) required rescue analgesia. No serious adverse events, local anesthetic systemic toxicity, pneumothorax, or neurological complications occurred.</p><p><strong>Conclusion: </strong>The EC50 of ropivacaine for TPVB in ESRD patients undergoing PDC was approximately 0.17%-0.18%, with favorable early recovery and acceptable safety. Given that EC50 reflects efficacy in only 50% of patients, EC90/EC95 studies are needed before definitive dosing recommendations.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"638060"},"PeriodicalIF":6.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105696","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":"Prior Use of GLP-1 Receptor Agonists versus SGLT2 Inhibitors and Clinical Outcomes After Sepsis in Patients with Type 2 Diabetes: A Propensity Score-Matched Cohort Study.","authors":"Hao-Hsun Liu, Sheng-Chi Huang, Jheng-Yan Wu, Khee-Siang Chan, Chih-Cheng Lai","doi":"10.2147/DDDT.S642220","DOIUrl":"https://doi.org/10.2147/DDDT.S642220","url":null,"abstract":"<p><strong>Background: </strong>Whether pre-existing glucose-lowering therapy influences outcomes after sepsis remains uncertain. We compared clinical outcomes among patients with type 2 diabetes (T2D) who developed sepsis according to prior GLP-1 receptor agonists (GLP-1RAs) or SGLT2 inhibitors (SGLT2is) use.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adults with T2D who developed sepsis had received a GLP-1RA or an SGLT2i within 3 months before sepsis were identified. After 1:1 propensity score matching, 11,969 patients were included in each group. The primary outcome was 90-day all-cause mortality. Secondary outcomes included major adverse cardiovascular event (MACE), major adverse kidney event (MAKE), intensive care unit (ICU) admission, major adverse cardiac and cerebrovascular event (MACCE), septic shock, and acute respiratory failure.</p><p><strong>Results: </strong>Compared with prior SGLT2i use, prior GLP-1RA use was associated with lower 90-day all-cause mortality (incidence rate, 48.6 vs 60.6 per 100 person-years; HR, 0.81; 95% CI, 0.75-0.88; E-value: 1.6) and lower risks of MACE (HR, 0.77; 0.65-0.91; E-value, 1.7), myocardial infarction (HR, 0.82; 0.67-0.99; E-value, 1.7), ICU admission (HR, 0.89; 0.84-0.94; E-value, 1.4), and MACCE (HR, 0.86; 0.74-0.99; E-value, 1.5). No significant difference was observed for septic shock (HR, 0.87; 95% CI, 0.74-1.02), acute respiratory failure (HR, 0.94; 95% CI, 0.83-1.06), or MAKE (HR, 1.08; 95% CI, 0.92-1.27). The mortality benefit remained consistent through 365 days and across all prespecified subgroups. After Holm correction for multiple comparisons across the seven secondary outcomes, only the associations with MACE (adjusted P=0.012) and ICU admission (adjusted P<0.007) remained statistically significant, while those with MACCE, myocardial infarction, MAKE, septic shock, and acute respiratory failure did not.</p><p><strong>Conclusion: </strong>Among patients with T2D who developed sepsis, prior GLP-1RA use was associated with lower mortality and select cardiovascular/renal risks than prior SGLT2i use, though roughly half of secondary outcomes showed no significant difference. Exposure was defined at the drug-class rather than individual-agent level, and modest E-values alongside baseline imbalances before matching suggest residual confounding cannot be excluded. These hypothesis-generating findings warrant confirmation in prospective studies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"20 ","pages":"642220"},"PeriodicalIF":6.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105236","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}