Clinical therapeutics最新文献

{"title":"Real-world Impact of GLP-1 Receptor Agonists on Health-related Quality of Life in Type 2 Diabetes and Obesity (SEVERAL Study).","authors":"José Seijas-Amigo, Ángel Salgado-Barreira, Carlota Roca-Martinez, Rosana Castelo-Dominguez, María Teresa Pérez-Álvarez, Belén Ponce-Piñón, Marlén Fernández-Silva, Marta Rodríguez-Barreiro, Mercedes Pereira-Pía, Jose Manuel Iglesias-Moreno, Mar Gago-García, Raquel Montáns-García, Agustina Fernandez-Perez, Dolores Fraga-Gayoso, Montse Fernandez-Montenegro, Beatriz Riveiro-Barciela, Natalia Rilla-Villar, Begoña Cardeso-Paredes, Marta Ribeiro-Ferreiro, Diego Rodriguez-Penas, Alberto Cordero, Moisés Rodríguez-Mañero, José R González-Juanatey","doi":"10.1016/j.clinthera.2026.03.012","DOIUrl":"https://doi.org/10.1016/j.clinthera.2026.03.012","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the real-world impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on health-related quality of life (HRQoL) and metabolic outcomes in adults with type 2 diabetes and obesity.</p><p><strong>Methods: </strong>We conducted a multicenter prospective cohort study across 13 primary-care centers in Spain. Adults with type 2 diabetes and body mass index (BMI) > 30 kg/m² initiating a GLP-1 RA were followed for 44 weeks. Baseline and week-44 assessments included anthropometric and biochemical parameters and HRQoL measured using the EQ-5D index and visual analogue scale (VAS), and the SF-12 physical and mental component summaries (PCS/MCS). Changes were analyzed using paired statistical tests overall and by achievement of ≥5% weight loss.</p><p><strong>Findings: </strong>Among 135 patients, significant improvements were observed in glucose, HbA1c, LDL-C, waist circumference, body weight, and BMI. HRQoL improved in EQ-5D domains including mobility, pain/discomfort, and anxiety/depression. The EQ-5D index increased from 0.71 to 0.79 (P < 0.001), and VAS from 58.3 to 65.3 (P = 0.007). SF-12 PCS improved significantly, whereas MCS showed no overall change. Patients achieving ≥5% weight loss experienced greater improvements in EQ-5D index, VAS, and PCS. Subcutaneous and oral semaglutide improved the EQ-5D index; oral semaglutide improved VAS and MCS; and subcutaneous semaglutide improved PCS.</p><p><strong>Implications: </strong>In routine clinical practice, GLP-1 RAs were associated with clinically meaningful improvements in HRQoL and metabolic outcomes, particularly when ≥5% weight loss is achieved, supporting the integration of patient-reported outcomes into diabetes and obesity management. TRIAL REGISTRATION CLINICALTRIALS.</p><p><strong>Gov identifier: </strong>NCT05136287.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Efficacy and Safety of Combination Therapy With Low Dose of Telmisartan and S-Amlodipine in Patients With Hypertension: A Randomized, Double-Blind, Multicenter, Therapeutic Confirmatory, Phase III Clinical Trial\".","authors":"Swarupanjali Padhi, Prashant Ramdas Kokiwar, Janvi Patel, Ankita Kalra","doi":"10.1016/j.clinthera.2026.04.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2026.04.004","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding \"Efficacy and Safety of Combination Therapy With Low Dose of Telmisartan and S-Amlodipine in Patients With Hypertension: A Randomized, Double-Blind, Multicenter, Therapeutic Confirmatory, Phase III Clinical Trial\".","authors":"Beijia Yan","doi":"10.1016/j.clinthera.2026.04.005","DOIUrl":"https://doi.org/10.1016/j.clinthera.2026.04.005","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in Personalized Breast Cancer Drug Safety: From Preclinical Toxicology to Clinical Risk Management","authors":"Jayashree Venugopal PhD ,&nbsp;Surabhi Panneerselvam ,&nbsp;Afroz Patan PhD ,&nbsp;Panneerselvam Theivendren PhD","doi":"10.1016/j.clinthera.2026.03.002","DOIUrl":"10.1016/j.clinthera.2026.03.002","url":null,"abstract":"<div><h3>Purpose</h3><div>The artificial intelligence (AI) implementation in personalized medicine has transformed drug safety, especially in breast cancer treatment. The importance of the need to treat breast cancer individually is acute as the disorder is heterogeneous and reacts differently to the use of chemotherapeutic agents.</div></div><div><h3>Methods</h3><div>Use of AI technologies including machine learning algorithms, deep learning, and predictive analytics can be used to acknowledge the presence of any possible toxicological risks in the early drug development stages to enhance efficacy and safety of therapies.</div></div><div><h3>Findings</h3><div>The strategies can be used to tailor treatment according to the genetic, molecular, and clinical features of a patient and minimize adverse drug reactions and maximize outcomes. The promise in the application of AI to predict treatment responses, optimize drug dosages, and ensure long-term safety through the combination of clinical trials, patient records, and real-world evidence has been high.</div></div><div><h3>Implications</h3><div>Throughout this review, it has been shown that AI can transform preclinical toxicology, clinical trial design, and postmarketing surveillance and overcome challenges and opportunities in the expanding area of drug development in breast cancer <span><span>https://clinicaltrials.gov/</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 5","pages":"Pages 449-461"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Safety for Lactating Women: Still a Forgotten Frontier?","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2026.04.001","DOIUrl":"10.1016/j.clinthera.2026.04.001","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 5","pages":"Pages 397-398"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YUVIWELⓇ (navepegritide)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2026.03.021","DOIUrl":"10.1016/j.clinthera.2026.03.021","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 5","pages":"Pages 480-482"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Ethnicity Assessment of Ribociclib Pharmacokinetics in Patients With Early and Advanced Breast Cancer","authors":"Yan Ji PhD ,&nbsp;Feng Sun PhD ,&nbsp;Masahiko Sato PhD ,&nbsp;Satoru Inoue MSc ,&nbsp;Yolanda Bi MSc ,&nbsp;Juan Pablo Zarate MD, PhD ,&nbsp;Yen-Shen Lu MD, PhD","doi":"10.1016/j.clinthera.2026.03.004","DOIUrl":"10.1016/j.clinthera.2026.03.004","url":null,"abstract":"<div><h3>Background</h3><div>Pharmacokinetics (PK) ethnicity assessment of ribociclib, a selective CDK4/6 inhibitor approved in combination with endocrine therapy for HR+/HER2– early breast cancer (eBC) and advanced breast cancer (aBC), in Asian and global patients is presented.</div></div><div><h3>Method</h3><div>PK data were analyzed from six global and three Asian studies: a phase 1 study of advanced solid tumors or lymphomas (X2101), a phase 1b/2 aBC study (X2107), three pivotal phase 3 aBC studies (MONALEESA-2/-3/-7), a pivotal phase 3 eBC study (NATALEE), a Japanese phase 1 study in advanced tumors (X1101), an Asian phase 2 aBC study (MONALEESASIA), and a phase 2 Chinese aBC study (A2206).</div></div><div><h3>Results</h3><div>PK parameters from global and Asian studies were collected. At 600 mg ribociclib, PK exposure (area under the curve, maximum concentration, trough concentration) in Asian studies (MONALEESASIA, A2206) was comparable with that seen in global studies (X2101, X2107, MONALEESA-2/-3/-7) in advanced cancer and aBC. The PK exposure range in Japanese patients in X1101 and MONALEESASIA was largely comparable with that in non-Japanese Asian patients in MONALEESASIA and global patients (X2101) at both 400 and 600 mg doses of ribociclib. Intrastudy analyses of MONALEESA-3/-7 and NATALEE further suggested comparable PK exposure between Asian and non-Asian patients with aBC and eBC.</div></div><div><h3>Conclusions</h3><div>This comprehensive ethnicity assessment suggests comparable PK of ribociclib between Asian and non-Asian patients and supports current dose recommendations in Asian patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 5","pages":"Pages 407-417"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Weight and Renal Function: DOAC Plasma Levels Remain the Primary Determinant of Acute Outcomes—A Re-Analysis of the 4Levels Study","authors":"Riccardo Mazza MD ,&nbsp;Carlo Gaspardone MD ,&nbsp;Chiara Miranda ,&nbsp;Sofia Di Bisceglie ,&nbsp;Alessia Minerva MD ,&nbsp;Rachele Sena MD ,&nbsp;Gianmarco Cozzani MD ,&nbsp;Anna Salerno MD ,&nbsp;Michela Cera MD ,&nbsp;Massimo Slavich MD ,&nbsp;Leila Anna De Lorenzo MD ,&nbsp;Giulio Leo MD ,&nbsp;Giulia Nemola MD ,&nbsp;Annalisa Fattorini MD ,&nbsp;Luciano Crippa MD ,&nbsp;Patrizia Della Valle MD ,&nbsp;Alberto Margonato MD ,&nbsp;Armando D’Angelo MD ,&nbsp;Cosmo Godino MD ,&nbsp;4Levels Study Investigators","doi":"10.1016/j.clinthera.2026.03.008","DOIUrl":"10.1016/j.clinthera.2026.03.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 5","pages":"Pages 471-474"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “New Drug Capsule BLUJEPA (gepotidacin)” [Clin Ther. 2026;48:291–293]","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2026.03.024","DOIUrl":"10.1016/j.clinthera.2026.03.024","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 5","pages":"Page 483"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Cotinine–Defined Tobacco Exposure and Its Association With Stroke, Mortality, and Cognitive Outcomes: Evidence From NHANES 2003 to 2018","authors":"Pengtao Qin MSc ,&nbsp;Rongrong Chen MSc ,&nbsp;Hongyan Zhang BS ,&nbsp;Zhuo Li BS ,&nbsp;Chongli Zhang MSc ,&nbsp;Ying Wang MSc ,&nbsp;Liujun Chang BS","doi":"10.1016/j.clinthera.2026.03.009","DOIUrl":"10.1016/j.clinthera.2026.03.009","url":null,"abstract":"<div><h3>Purpose</h3><div>To examine the association between serum cotinine—an objective biomarker of recent tobacco smoke exposure from active smoking and secondhand smoke—and stroke, all-cause mortality, and cognitive outcomes among US adults using National Health and Nutrition Examination Survey (NHANES) 2003 to 2018 data.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional analysis of NHANES 2003 to 2018. Serum cotinine was categorized into quartiles and also evaluated per interquartile range (IQR) increase. All analyses accounted for the complex NHANES sampling design (weights, strata, and primary sampling units). Associations with stroke were examined using survey-weighted multivariable logistic regression. Mortality outcomes from NHANES-linked mortality files were evaluated using survey-weighted Cox proportional hazards models and Kaplan–Meier curves with log-rank tests; these analyses were interpreted as associational. Cognitive outcomes were dichotomized using test-specific 25th-percentile cutoffs and analyzed using survey-weighted logistic regression; ORs represent the odds of preserved cognition (≥25th percentile). Prespecified subgroup analyses (by sex, race/ethnicity, education, and Composite Dietary Antioxidant Index) were conducted, and multiplicative interaction terms were tested.</div></div><div><h3>Findings</h3><div>A total of 8285 participants were included, of whom 592 reported a physician diagnosis of stroke. Per IQR increase in serum cotinine, higher cotinine was associated with higher odds of stroke (OR 1.50, 95% CI 1.19–1.90). Among participants with stroke, higher cotinine was associated with higher all-cause mortality (per IQR increase: HR 1.30, 95% CI 1.08–1.56). Higher cotinine was also associated with lower odds of preserved cognition on Animal Fluency Test and CERAD (OR 0.67, 95% CI 0.62–0.73; OR 0.94, 95% CI 0.89–0.99, respectively). In exploratory subgroup analyses, associations appeared stronger in women and non-Hispanic White participants.</div></div><div><h3>Implications</h3><div>Higher serum cotinine levels were associated with stroke, all-cause mortality among individuals with stroke, and cognitive impairment in NHANES 2003 to 2018. These findings are observational and do not establish causality; prospective studies are warranted to clarify temporality and to evaluate the effects of tobacco exposure reduction or cessation interventions on stroke-related outcomes.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 5","pages":"Pages 426-431"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}