Pub Date : 2025-12-01DOI: 10.1016/j.clinthera.2025.09.005
Anastasia Uster MD , Nihar Desai MD , Sankar D. Navaneethan MD , Egon Pfarr MSc , Anna Rita Mazo MD
Purpose
Chronic kidney disease (CKD) increases hospitalization risk. In the randomized, phase III, EMPA-KIDNEY trial, empagliflozin significantly reduced risk of all-cause hospitalizations (ACH; first and recurrent) vs placebo. This post hoc analysis of the EMPA-KIDNEY trial examines the burden of ACH in CKD and the effects of empagliflozin on ACH.
Methods
Participants with CKD (n = 6609) were randomized to empagliflozin 10 mg or placebo. Reasons for hospitalizations were derived from adverse events leading to hospitalization, assessed by system organ class.
Findings
Overall, 1995 participants (1035 placebo, 960 empagliflozin) had ≥1 ACH (1895 ACH in placebo and 1611 in the empagliflozin 10-mg groups). The estimated mortality rate after first hospitalization in participants with ≥1 hospitalization was 12% after 1 year and 18% after 2 years, and risk of death was ∼10 times higher vs those without (hazard ratio [HR] 9.53; 95% confidence interval [CI], 7.18–12.64; P < 0.0001). The most common reasons for hospitalization were infections and infestations, surgical and medical procedures, investigations, cardiac disorders, renal and urinary disorders, and metabolic disorders. Risk of ACH was significantly reduced for empagliflozin vs placebo (HR: 0.86, 95% CI, 0.78–0.95, P = 0.003). This was consistent regardless of baseline diabetes status, estimated glomerular filtration rate, or urinary albumin-to-creatinine ratio. Mean cumulative incidence of ACH in empagliflozin and placebo groups diverged shortly after randomization and separated further over time. Risk of hospital admissions from cardiovascular (CV), renal, or metabolic conditions was significantly lower with empagliflozin vs placebo (P < 0.05).
Implications
Treatment with empagliflozin significantly reduced risk of ACH, including those attributed to CV, renal, or metabolic conditions.
{"title":"Empagliflozin Reduces Risk of Hospitalization in Patients With Chronic Kidney Disease in the EMPA-KIDNEY Trial","authors":"Anastasia Uster MD , Nihar Desai MD , Sankar D. Navaneethan MD , Egon Pfarr MSc , Anna Rita Mazo MD","doi":"10.1016/j.clinthera.2025.09.005","DOIUrl":"10.1016/j.clinthera.2025.09.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Chronic kidney disease (CKD) increases hospitalization risk. In the randomized, phase III, EMPA-KIDNEY trial, empagliflozin significantly reduced risk of all-cause hospitalizations (ACH; first and recurrent) vs placebo. This post hoc analysis of the EMPA-KIDNEY trial examines the burden of ACH in CKD and the effects of empagliflozin on ACH.</div></div><div><h3>Methods</h3><div>Participants with CKD (n = 6609) were randomized to empagliflozin 10 mg or placebo. Reasons for hospitalizations were derived from adverse events leading to hospitalization, assessed by system organ class.</div></div><div><h3>Findings</h3><div>Overall, 1995 participants (1035 placebo, 960 empagliflozin) had ≥1 ACH (1895 ACH in placebo and 1611 in the empagliflozin 10-mg groups). The estimated mortality rate after first hospitalization in participants with ≥1 hospitalization was 12% after 1 year and 18% after 2 years, and risk of death was ∼10 times higher vs those without (hazard ratio [HR] 9.53; 95% confidence interval [CI], 7.18–12.64; <em>P</em> < 0.0001). The most common reasons for hospitalization were infections and infestations, surgical and medical procedures, investigations, cardiac disorders, renal and urinary disorders, and metabolic disorders. Risk of ACH was significantly reduced for empagliflozin vs placebo (HR: 0.86, 95% CI, 0.78–0.95, <em>P</em> = 0.003). This was consistent regardless of baseline diabetes status, estimated glomerular filtration rate, or urinary albumin-to-creatinine ratio. Mean cumulative incidence of ACH in empagliflozin and placebo groups diverged shortly after randomization and separated further over time. Risk of hospital admissions from cardiovascular (CV), renal, or metabolic conditions was significantly lower with empagliflozin vs placebo (<em>P</em> < 0.05).</div></div><div><h3>Implications</h3><div>Treatment with empagliflozin significantly reduced risk of ACH, including those attributed to CV, renal, or metabolic conditions.</div></div><div><h3>ClinicalTrials.gov number</h3><div>NCT03594110</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1091-1096"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231496","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}
Pub Date : 2025-12-01DOI: 10.1016/j.clinthera.2025.09.010
Li Wang PhD, Xiangyun Jin MS, YanChun Li MS
Purpose
To investigate whether fenofibrate use is associated with an increased risk of renal and urinary adverse events based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).
Methods
This retrospective pharmacovigilance study utilized data from the FAERS between January 1st, 2019, and December 31st, 2023. Reports listing fenofibrate as the primary suspect drug were extracted, and renal and urinary adverse events were identified based on preferred terms (PTs) in the MedDRA dictionary. Disproportionality analysis was conducted using four standard algorithms—reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS)—to detect safety signals. The PTs exhibiting positive signals were clinically prioritized, and bivariate logistic regression analysis was performed to identify demographic risk factors associated with serious clinical outcomes.
Findings
Between 1 January 2019 and 31 December 2023, a total of 2,810 adverse event reports related to fenofibrate were identified, of which 443 (15.77%) were classified as renal and urinary adverse events. The mean age of affected patients was 57.89 years, with a higher proportion of males (n = 183, 27.94%). Signal detection showed a significant association between fenofibrate and renal and urinary adverse events: ROR = 2.23 (95% CI:2.07–2.41), PRR = 2.18 (χ² = 428.29), IC = 1.12 (IC025 = 1.01), EBGM = 2.18 (EBGM05 = 2.04). Adverse events reported with high frequency included acute kidney injury (n = 149, 22.29%), haematuria (n = 88, 13.44%), and urinary tract disorder (n = 82, 12.52%), with acute kidney injury and anuria identified as key clinical priority events. Bivariate logistic regression analysis demonstrated that individuals aged above 65 years had a significantly higher likelihood of experiencing serious clinical outcomes (OR = 2.046, 95% CI: 1.579–3.665; P < 0.001), males have a lower risk (OR = 0.656, 95% CI: 0.444–0.968, P = 0.034).
Implications
This study suggests a possible significant association between fenofibrate and renal and urinary adverse events. Safety monitoring and individualized risk assessment of patients using fenofibrate should be enhanced to reduce the risk of potential adverse outcomes.
{"title":"Characterizing Fenofibrate-Related Renal and Urinary Adverse Events: A Comprehensive Analysis of FDA Adverse Event Reporting System Database","authors":"Li Wang PhD, Xiangyun Jin MS, YanChun Li MS","doi":"10.1016/j.clinthera.2025.09.010","DOIUrl":"10.1016/j.clinthera.2025.09.010","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate whether fenofibrate use is associated with an increased risk of renal and urinary adverse events based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).</div></div><div><h3>Methods</h3><div>This retrospective pharmacovigilance study utilized data from the FAERS between January 1st, 2019, and December 31st, 2023. Reports listing fenofibrate as the primary suspect drug were extracted, and renal and urinary adverse events were identified based on preferred terms (PTs) in the MedDRA dictionary. Disproportionality analysis was conducted using four standard algorithms—reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS)—to detect safety signals. The PTs exhibiting positive signals were clinically prioritized, and bivariate logistic regression analysis was performed to identify demographic risk factors associated with serious clinical outcomes.</div></div><div><h3>Findings</h3><div>Between 1 January 2019 and 31 December 2023, a total of 2,810 adverse event reports related to fenofibrate were identified, of which 443 (15.77%) were classified as renal and urinary adverse events. The mean age of affected patients was 57.89 years, with a higher proportion of males (n = 183, 27.94%). Signal detection showed a significant association between fenofibrate and renal and urinary adverse events: ROR = 2.23 (95% CI:2.07–2.41), PRR = 2.18 (χ² = 428.29), IC = 1.12 (IC<sub>025</sub> = 1.01), EBGM = 2.18 (EBGM05 = 2.04). Adverse events reported with high frequency included acute kidney injury (n = 149, 22.29%), haematuria (n = 88, 13.44%), and urinary tract disorder (n = 82, 12.52%), with acute kidney injury and anuria identified as key clinical priority events. Bivariate logistic regression analysis demonstrated that individuals aged above 65 years had a significantly higher likelihood of experiencing serious clinical outcomes (OR = 2.046, 95% CI: 1.579–3.665; <em>P < 0.</em>001), males have a lower risk (OR = 0.656, 95% CI: 0.444–0.968, <em>P = 0.</em>034).</div></div><div><h3>Implications</h3><div>This study suggests a possible significant association between fenofibrate and renal and urinary adverse events. Safety monitoring and individualized risk assessment of patients using fenofibrate should be enhanced to reduce the risk of potential adverse outcomes.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1149-1154"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274013","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}
Pub Date : 2025-12-01DOI: 10.1016/j.clinthera.2025.10.001
Jinho Shin MD, PhD , SeongHwan Kim MD, PhD , KiHoon Han MD, PhD , MooHyun Kim MD, PhD , YoungKeun Ahn MD, PhD , IlSuk Sohn MD, PhD , KwangIl Kim MD, PhD , DongHun Cha MD, PhD , SoonJun Hong MD, PhD , EunJoo Cho MD, PhD , HaeYoung Lee MD, PhD , WookBum Pyun MD, PhD , HoJoong Youn MD, PhD , WooShik Kim MD, PhD , MooYong Rhee MD, PhD , JunHee Lee MD, PhD , JongWon Ha MD, PhD , JiYong Choi MD, PhD , ByungSu Yoo MD, PhD , JinOk Jeong MD, PhD , ChongJin Kim MD, PhD
<div><h3>Purpose</h3><div>Hypertension poses challenges for many patients in achieving adequate blood pressure control, despite using monotherapy or standard treatment regimens. A low-dose triple combination drug has recently been considered for initial hypertension therapy; however, its safety, efficacy, and dose-response relationship remain unclear. We evaluated these aspects for patients with hypertension to determine the optimal combination dose.</div></div><div><h3>Methods</h3><div>A multicenter, randomized, double-blind, parallel, phase 2 clinical trial was conducted in South Korea. Following a two-week placebo run-in period, 253 patients of SPC1001 were randomized into the High, Mid1, Mid2, and Low groups, which consisted of a fixed-dose triple combination of candesartan, amlodipine, and indapamide at varying doses. The dosages were SPC1001 High (4/2.5/1.25 mg), SPC1001 Mid1 (2.67/1.67/0.83 mg), SPC1001 Mid2 (4/1.25/1.25 mg), SPC1001 Low (2/1.25/0.625 mg), SPC3001 (candesartan 8 mg), SPC4001 (amlodipine 5 mg), SPC4002 (amlodipine 10 mg), and placebo, with the number of participants in the groups at a 1:1:1:1:1:1:1:1 ratio. Participants who had been using antihypertensive medication during the screening visit were required to discontinue it at least 4 weeks before the run-in period. The primary endpoint was determined by evaluating how mean sitting systolic blood pressure (MSSBP) varied between the baseline measurement and week 8. Treatment emergent adverse events and clinically significant changes on physical examination, including the assessment of ankle edema, laboratory tests, vital signs, and 12-lead electrocardiography, were also evaluated.</div></div><div><h3>Findings</h3><div>SPC1001 High and SPC1001 Mid2 were identified as the two groups with the most effective dosages. The least square mean difference (LSMD) of SPC1001 High compared to SPC3001, SPC4001, SPC4002, and placebo was –7.50, −7.68, 0.03, and −16.97 mm Hg, respectively (<em>P</em>-values for ANCOVA were 0.04, 0.0473, 0.9929, and <0.0001). The LSMD of SPC 1001 Mid2 compared with that of SPC3001, SPC4001, SPC4002, and placebo was −8.72, −8.72, −1.85, and −18.02 mm Hg, respectively (<em>P-values</em> for ANCOVA were 0.0075, 0.0119, 0.5704, and <0.0001). The LSMD of SPC 1001 Mid1 compared to that of SPC3001, SPC4001, SPC4002, and placebo was −4.90, −5.21, 3.03, and −14.44 mm Hg, respectively (<em>P</em>-values for ANCOVA were 0.1178, 0.1205, 0.3347, and <0.0001). The LSMD of SPC1001 Low compared to that of SPC3001, SPC4001, SPC4002, and placebo was −0.51, −0.87, 7.30, and −9.88 mm Hg, respectively (<em>P-values</em> for ANCOVA were 0.8799, 0.8088, 0.0284, and <0.0047). There were two serious adverse events recorded, in SPC1001 High and SPC3001.</div></div><div><h3>Implications</h3><div>Low-dose triple combination therapies may be effective for treating hypertension.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov identifier: NCT06212648.</div></
{"title":"Multicenter, Randomized, Double-Blind, Parallel, Phase 2 Clinical Trial to Compare and Evaluate the Efficacy and Safety of SPC1001 and Monotherapy in Patients With Essential Hypertension","authors":"Jinho Shin MD, PhD , SeongHwan Kim MD, PhD , KiHoon Han MD, PhD , MooHyun Kim MD, PhD , YoungKeun Ahn MD, PhD , IlSuk Sohn MD, PhD , KwangIl Kim MD, PhD , DongHun Cha MD, PhD , SoonJun Hong MD, PhD , EunJoo Cho MD, PhD , HaeYoung Lee MD, PhD , WookBum Pyun MD, PhD , HoJoong Youn MD, PhD , WooShik Kim MD, PhD , MooYong Rhee MD, PhD , JunHee Lee MD, PhD , JongWon Ha MD, PhD , JiYong Choi MD, PhD , ByungSu Yoo MD, PhD , JinOk Jeong MD, PhD , ChongJin Kim MD, PhD","doi":"10.1016/j.clinthera.2025.10.001","DOIUrl":"10.1016/j.clinthera.2025.10.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Hypertension poses challenges for many patients in achieving adequate blood pressure control, despite using monotherapy or standard treatment regimens. A low-dose triple combination drug has recently been considered for initial hypertension therapy; however, its safety, efficacy, and dose-response relationship remain unclear. We evaluated these aspects for patients with hypertension to determine the optimal combination dose.</div></div><div><h3>Methods</h3><div>A multicenter, randomized, double-blind, parallel, phase 2 clinical trial was conducted in South Korea. Following a two-week placebo run-in period, 253 patients of SPC1001 were randomized into the High, Mid1, Mid2, and Low groups, which consisted of a fixed-dose triple combination of candesartan, amlodipine, and indapamide at varying doses. The dosages were SPC1001 High (4/2.5/1.25 mg), SPC1001 Mid1 (2.67/1.67/0.83 mg), SPC1001 Mid2 (4/1.25/1.25 mg), SPC1001 Low (2/1.25/0.625 mg), SPC3001 (candesartan 8 mg), SPC4001 (amlodipine 5 mg), SPC4002 (amlodipine 10 mg), and placebo, with the number of participants in the groups at a 1:1:1:1:1:1:1:1 ratio. Participants who had been using antihypertensive medication during the screening visit were required to discontinue it at least 4 weeks before the run-in period. The primary endpoint was determined by evaluating how mean sitting systolic blood pressure (MSSBP) varied between the baseline measurement and week 8. Treatment emergent adverse events and clinically significant changes on physical examination, including the assessment of ankle edema, laboratory tests, vital signs, and 12-lead electrocardiography, were also evaluated.</div></div><div><h3>Findings</h3><div>SPC1001 High and SPC1001 Mid2 were identified as the two groups with the most effective dosages. The least square mean difference (LSMD) of SPC1001 High compared to SPC3001, SPC4001, SPC4002, and placebo was –7.50, −7.68, 0.03, and −16.97 mm Hg, respectively (<em>P</em>-values for ANCOVA were 0.04, 0.0473, 0.9929, and <0.0001). The LSMD of SPC 1001 Mid2 compared with that of SPC3001, SPC4001, SPC4002, and placebo was −8.72, −8.72, −1.85, and −18.02 mm Hg, respectively (<em>P-values</em> for ANCOVA were 0.0075, 0.0119, 0.5704, and <0.0001). The LSMD of SPC 1001 Mid1 compared to that of SPC3001, SPC4001, SPC4002, and placebo was −4.90, −5.21, 3.03, and −14.44 mm Hg, respectively (<em>P</em>-values for ANCOVA were 0.1178, 0.1205, 0.3347, and <0.0001). The LSMD of SPC1001 Low compared to that of SPC3001, SPC4001, SPC4002, and placebo was −0.51, −0.87, 7.30, and −9.88 mm Hg, respectively (<em>P-values</em> for ANCOVA were 0.8799, 0.8088, 0.0284, and <0.0047). There were two serious adverse events recorded, in SPC1001 High and SPC3001.</div></div><div><h3>Implications</h3><div>Low-dose triple combination therapies may be effective for treating hypertension.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov identifier: NCT06212648.</div></","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1113-1123"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400031","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}
This review is the first to assess the effects of green tea on blood pressure, lipid profile, and glucose in people with metabolic syndrome, highlighting its potential anti-inflammatory and metabolic benefits.
Methods
We used Standardized Mean Differences (SMD) and Cohen's d for group comparisons, while heterogeneity and publication bias were assessed using the I² statistic, Cochrane Q test, Begg’s funnel plot, and Egger’s test.
Results
Our results showed that green tea consumption did not significantly affect FBS (SMD: –0.03; 95%; P = 0.95), HbA1C (SMD: 4.87; 95%; P = 0.63), systolic blood pressure (SMD: -0.42; 95%; P = 0.36), diastolic blood pressure (SMD: –0.24; 95%; P = 0.53), total cholesterol (SMD: –0.38; 95%; P = 0.19), TG (SMD: –0.17; 95%; P = 0.34), HDL-C (SMD: –0.07; 95%; P = 0.75), or LDL-C (SMD: –0.45; 95%; P = 0.25). Subgroup analyses showed that short-term green tea intake (<8 weeks) significantly reduced FBS (SMD: –1.62), total cholesterol (SMD: –1.09), TG (SMD: –0.74), and LDL-C (SMD: -0.83). Doses below 3000 mg/day were also linked to lower total cholesterol (SMD: –0.69) and LDL-C (SMD: –0.83). Among women, green tea improved total cholesterol (SMD: –0.79), HDL-C (SMD: 0.50), LDL-C (SMD: –1.25), and systolic blood pressure (SMD: –1.74), despite overall high heterogeneity and publication bias.
Conclusion
Although our results found no significant difference in the measurement factor in patients with MetS. subgroup analyses suggested potential benefits in women, those consuming lower doses (<3000 mg/day), and those with shorter intervention durations (<8 weeks).
本综述首次评估了绿茶对代谢综合征患者血压、血脂和血糖的影响，强调了其潜在的抗炎和代谢益处。方法：采用标准化平均差异（SMD）和Cohen’s d进行组间比较，采用I²统计量、Cochrane Q检验、Begg’s漏斗图和Egger’s检验评估异质性和发表偏倚。结果：我们的研究结果显示，绿茶摄入对FBS （SMD: -0.03; 95%; P = 0.95）、HbA1C （SMD: 4.87; 95%; P = 0.63）、收缩压（SMD: -0.42; 95%; P = 0.36）、舒张压（SMD: -0.24; 95%; P = 0.53）、总胆固醇（SMD: -0.38; 95%; P = 0.19）、TG （SMD: -0.17; 95%; P = 0.34）、HDL-C （SMD: -0.07; 95%; P = 0.75）或LDL-C （SMD: -0.45; 95%; P = 0.25）没有显著影响。亚组分析显示，短期绿茶摄入量(结论：尽管我们的研究结果在met患者的测量因子中没有发现显著差异。亚组分析显示，服用较低剂量的女性(
{"title":"The Association Between Green Tea Intake and Metabolic Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials","authors":"Sahar Ghoflchi , Hadiseh Mohammadi , Maryam Teimouri , Masoud Imani , Hossein Hosseini","doi":"10.1016/j.clinthera.2025.09.011","DOIUrl":"10.1016/j.clinthera.2025.09.011","url":null,"abstract":"<div><h3>Introduction</h3><div>This review is the first to assess the effects of green tea on blood pressure, lipid profile, and glucose in people with metabolic syndrome, highlighting its potential anti-inflammatory and metabolic benefits<strong>.</strong></div></div><div><h3>Methods</h3><div>We used Standardized Mean Differences (SMD) and Cohen's d for group comparisons, while heterogeneity and publication bias were assessed using the I² statistic, Cochrane Q test, Begg’s funnel plot, and Egger’s test.</div></div><div><h3>Results</h3><div>Our results showed that green tea consumption did not significantly affect FBS (SMD: –0.03; 95%; <em>P = 0.</em>95), HbA1C (SMD: 4.87; 95%; <em>P = 0.</em>63), systolic blood pressure (SMD: -0.42; 95%; <em>P = 0.</em>36), diastolic blood pressure (SMD: –0.24; 95%; <em>P = 0.</em>53), total cholesterol (SMD: –0.38; 95%; <em>P = 0.</em>19), TG (SMD: –0.17; 95%; <em>P = 0.</em>34), HDL-C (SMD: –0.07; 95%; <em>P = 0.</em>75), or LDL-C (SMD: –0.45; 95%; <em>P = 0.</em>25). Subgroup analyses showed that short-term green tea intake (<8 weeks) significantly reduced FBS (SMD: –1.62), total cholesterol (SMD: –1.09), TG (SMD: –0.74), and LDL-C (SMD: -0.83). Doses below 3000 mg/day were also linked to lower total cholesterol (SMD: –0.69) and LDL-C (SMD: –0.83). Among women, green tea improved total cholesterol (SMD: –0.79), HDL-C (SMD: 0.50), LDL-C (SMD: –1.25), and systolic blood pressure (SMD: –1.74), despite overall high heterogeneity and publication bias.</div></div><div><h3>Conclusion</h3><div>Although our results found no significant difference in the measurement factor in patients with MetS. subgroup analyses suggested potential benefits in women, those consuming lower doses (<3000 mg/day), and those with shorter intervention durations (<8 weeks).</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages e1-e9"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274133","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 “Real-World Polypharmacy and Drug–Drug Interactions in a Large Cohort of Direct Oral Anticoagulant Users With Atrial Fibrillation”","authors":"Xuezheng Zhu MBBS , Daquan Liao MBBS , Shiye Huang MBBS , Ziye Zhuang MBBS","doi":"10.1016/j.clinthera.2025.10.003","DOIUrl":"10.1016/j.clinthera.2025.10.003","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1180-1181"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430332","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}
Pub Date : 2025-12-01DOI: 10.1016/j.clinthera.2025.09.008
Brian Shiner MD, MPH , Bradley V. Watts MD, MPH , Luke Rozema MS , Jaimie L. Gradus DMSc, DSc, MPH
Purpose
Newer medications for Hepatitis C Virus Infection (HCV), called direct acting antivirals (DAAs), are less likely to cause depression than older interferon-containing treatments. However, the risk of exacerbating depression has not been examined in subgroups of patients with pre-existing mental illness. We investigated whether several DAAs for HCV, including glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL), impact depressive symptoms in a population of patients with post-traumatic stress disorder (PTSD).
Methods
We developed a retrospective cohort of United States Department of Veterans Affairs (VA) patients with PTSD receiving DAAs for HCV. We measured depressive symptoms before and after DAA treatment using the Patient Health Questionare-9 (PHQ-9), a patient-reported outcome measure with a range of 0-27, a screening threshold of 10 or higher, and a minimal clinically important difference of 5 points. We measured pre/post changes in PHQ-9 score and compared adjusted differences between treatment groups.
Findings
Our cohort included 873 patients (GLE/PIB n = 357, LDV/SOF n = 308, SOF/VEL n = 208). Adjusted baseline PHQ-9 scores were consistent with mild depression and similar across groups (10.5 ± 7.2 for GLE/PIB, 10.6 ± 7.2 for LDV/SOF, 10.9 ± 7.2 for SOF/VEL). Adjusted change in PHQ-9 score was minimal and did not differ across groups (-2.0 ± 5.8 for GLE/PIB, -1.1 ± 6.5 for LDV/SOF, -2.2 ± 6.1 for SOF/VEL). The adjusted frequency of 5-pont change was low and did not differ meaningfully across groups (Improvement: 22.4% for GLE/PIB, 18.9% for LDV/SOF, 26.6% for SOF/VEL; Worsening: 9.1% for GLE/PIB, 14.3% for LDV/SOF, 10.1% for SOF/VEL).
Implications
DAAs had very little impact on depressive symptoms for VA patients with PTSD and HCV infection.
{"title":"Comparative Effectiveness of Direct-Acting Antiviral Treatment for Hepatitis C Virus Infection on Depressive Symptoms in Patients With Posttraumatic Stress Disorder","authors":"Brian Shiner MD, MPH , Bradley V. Watts MD, MPH , Luke Rozema MS , Jaimie L. Gradus DMSc, DSc, MPH","doi":"10.1016/j.clinthera.2025.09.008","DOIUrl":"10.1016/j.clinthera.2025.09.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Newer medications for Hepatitis C Virus Infection (HCV), called direct acting antivirals (DAAs), are less likely to cause depression than older interferon-containing treatments. However, the risk of exacerbating depression has not been examined in subgroups of patients with pre-existing mental illness. We investigated whether several DAAs for HCV, including glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL), impact depressive symptoms in a population of patients with post-traumatic stress disorder (PTSD).</div></div><div><h3>Methods</h3><div>We developed a retrospective cohort of United States Department of Veterans Affairs (VA) patients with PTSD receiving DAAs for HCV. We measured depressive symptoms before and after DAA treatment using the Patient Health Questionare-9 (PHQ-9), a patient-reported outcome measure with a range of 0-27, a screening threshold of 10 or higher, and a minimal clinically important difference of 5 points. We measured pre/post changes in PHQ-9 score and compared adjusted differences between treatment groups.</div></div><div><h3>Findings</h3><div>Our cohort included 873 patients (GLE/PIB <em>n</em> = 357, LDV/SOF <em>n</em> = 308, SOF/VEL <em>n</em> = 208). Adjusted baseline PHQ-9 scores were consistent with mild depression and similar across groups (10.5 ± 7.2 for GLE/PIB, 10.6 ± 7.2 for LDV/SOF, 10.9 ± 7.2 for SOF/VEL). Adjusted change in PHQ-9 score was minimal and did not differ across groups (-2.0 ± 5.8 for GLE/PIB, -1.1 ± 6.5 for LDV/SOF, -2.2 ± 6.1 for SOF/VEL). The adjusted frequency of 5-pont change was low and did not differ meaningfully across groups (Improvement: 22.4% for GLE/PIB, 18.9% for LDV/SOF, 26.6% for SOF/VEL; Worsening: 9.1% for GLE/PIB, 14.3% for LDV/SOF, 10.1% for SOF/VEL).</div></div><div><h3>Implications</h3><div>DAAs had very little impact on depressive symptoms for VA patients with PTSD and HCV infection.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1137-1142"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205628","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}
Pub Date : 2025-12-01DOI: 10.1016/j.clinthera.2025.10.010
Paul Beninger MD, MBA
{"title":"Diabetes Mellitus: Promising Clinical Research in a Time of Political Uncertainty","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.10.010","DOIUrl":"10.1016/j.clinthera.2025.10.010","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1089-1090"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562929","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":"Constructive Critique on “Efficacy and Safety of Nintedanib in Japanese Patients With Early-Stage Idiopathic Pulmonary Fibrosis: A One-Year Interim Analysis from a Multicenter Observational Study in Kyushu and Okinawa, Japan”","authors":"Parth Aphale PhD, Himanshu Shekhar BHMS, Shashank Dokania BHMS","doi":"10.1016/j.clinthera.2025.08.009","DOIUrl":"10.1016/j.clinthera.2025.08.009","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1176-1177"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999849","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}
Pub Date : 2025-12-01DOI: 10.1016/j.clinthera.2025.09.009
Changjiang Wang BPharm , Yingshi Wang BMed , Wenwen Zheng MMed , Junli Wu BMed , Yufen Shen MMed , Jianjun Ji MPharm , Pengfei Du MMed
Purpose
To identify teplizumab-related adverse events (AEs) for type 1 diabetes mellitus from the United States Food and Drug Administration (US FDA) Adverse Event Reporting System database, enhancing the understanding of teplizumab safety in clinical settings.
Methods
AEs were extracted from the US FDA Adverse Event Reporting System database spanning from 2004Q1 to 2024Q4. The reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation, neural network, and empirical Bayes geometric mean methods were used to ensure the robustness of the adverse reaction signals.
Findings
A total of 847 AEs were identified, and 34 significant disproportionate preferred terms that met the requirements of 4 methods were obtained, involving 9 system categories. The most affected system organ classes were skin and subcutaneous tissue disorders (ROR = 3.24; 95% CI, 2.69–3.9), investigations (ROR = 2.77; 95% CI, 2.30–3.34), gastrointestinal disorders (ROR = 1.83; 95% CI, 1.51–2.21), and general disorders and administration site conditions (ROR = 1.43; 95% CI, 1.21–1.67) ranking by the ROR signal strength. The median time to onset of teplizumab-related AEs was 3.77 days (interquartile range = 0.00–4.00 days), and most AEs occurred within the first 30 days.
Implications
This study offers an enhanced comprehension of the potential AEs that could be induced by teplizumab, thereby furnishing invaluable insights for its clinical application.
{"title":"Assessment of Adverse Events of Teplizumab: A Real-world Pharmacovigilance Study Based on the FDA Adverse Event Reporting System","authors":"Changjiang Wang BPharm , Yingshi Wang BMed , Wenwen Zheng MMed , Junli Wu BMed , Yufen Shen MMed , Jianjun Ji MPharm , Pengfei Du MMed","doi":"10.1016/j.clinthera.2025.09.009","DOIUrl":"10.1016/j.clinthera.2025.09.009","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify teplizumab-related adverse events (AEs) for type 1 diabetes mellitus from the United States Food and Drug Administration (US FDA) Adverse Event Reporting System database, enhancing the understanding of teplizumab safety in clinical settings.</div></div><div><h3>Methods</h3><div>AEs were extracted from the US FDA Adverse Event Reporting System database spanning from 2004Q1 to 2024Q4. The reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation, neural network, and empirical Bayes geometric mean methods were used to ensure the robustness of the adverse reaction signals.</div></div><div><h3>Findings</h3><div>A total of 847 AEs were identified, and 34 significant disproportionate preferred terms that met the requirements of 4 methods were obtained, involving 9 system categories. The most affected system organ classes were skin and subcutaneous tissue disorders (ROR = 3.24; 95% CI, 2.69–3.9), investigations (ROR = 2.77; 95% CI, 2.30–3.34), gastrointestinal disorders (ROR = 1.83; 95% CI, 1.51–2.21), and general disorders and administration site conditions (ROR = 1.43; 95% CI, 1.21–1.67) ranking by the ROR signal strength. The median time to onset of teplizumab-related AEs was 3.77 days (interquartile range = 0.00–4.00 days), and most AEs occurred within the first 30 days.</div></div><div><h3>Implications</h3><div>This study offers an enhanced comprehension of the potential AEs that could be induced by teplizumab, thereby furnishing invaluable insights for its clinical application.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1143-1148"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291435","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号