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PubMed2026

Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JMKX003002 in Chinese healthy participants: a randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food-effect phase I clinical trial.

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharma-codynamics (PD) of the sodium-hydrogen exchanger 3 (NHE3) inhibitor JMKX003002 in Chinese healthy participants. PATIENTS AND METHODS: This phase I, randomized, double-blind, placebo-controlled study included a single-ascending dose (SAD) study with seven cohorts (1 mg [n = 4] and 5, 20, 50, 75, 100, or 125 mg [n = 8]), a food-effect (FE) study with six sequence groups (25 mg twice daily, n = 4), and a multiple-ascending dose (MAD) study with two cohorts (10 mg or 20 mg twice daily, n = 10). RESULTS: JMKX003002 was well-tolerated, with mostly mild treatment-related adverse events. One Grade 3 diarrhoea occurred in each of the 50 mg and 125 mg groups. No serious adverse events were reported, and no participants discontinued or withdrew due to treatment-emergent adverse events. Most plasma samples were below the limit of quantification (0.2 ng/mL), with only transient detection of low concentrations, indicating low systemic exposure. JMKX003002 was primarily excreted in stool (79.9% recovered) and was undetectable in urine. The PD results consistently showed decreased urinary sodium and phosphorus, along with increased stool sodium and phosphorus, compared to baseline across all three studies. One day after discontinuation, stool sodium and phosphorus remained elevated relative to baseline in the MAD study. Mixed-effects model analysis in the FE study demonstrated significant food effect on stool sodium and phosphorus excretion. CONCLUSION: JMKX003002 exhibited favorable safety and tolerability with minimal systemic exposure. It effectively increased sodium and phosphorus excretion in stool. These promising findings warrant further investigation of JMKX003002 to evaluate its clinical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070473). Registered on April 13, 2023; prospectively registered.

Adult↗

PubMed2026

Comparative efficacy and safety of pharmacokinetically guided and body surface area-based 5-fluorouracil dosing in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Body surface area (BSA)-based 5-fluorouracil (5-FU) dosing remains the standard in colorectal cancer despite substantial interpatient pharmacokinetic variability, which may lead to underexposure, treatment failure, or severe toxicity. This systematic review and meta-analysis evaluated whether pharmacokinetically guided 5-FU dosing improves efficacy and safety compared with conventional BSA-based dosing. METHODS: PubMed/MEDLINE, Embase, and Scopus databases were searched from inception to the final search date. The search identified 1,802 records: PubMed/MEDLINE, 47; Embase, 118; and Scopus, 1,637 records. Comparative randomized and non-randomized studies evaluating pharmacokinetically guided, area under the curve-guided, or therapeutic drug monitoring-based 5-FU dosing versus BSA-based dosing in colorectal cancer were included. Random-effects models were employed. The risk of bias was assessed using RoB 2 and ROBINS-I, and the certainty of evidence was evaluated using GRADE. RESULTS: Five studies comprising 809 unique patients were included. Across the primary severe-toxicity analysis, the pooled denominator was 1,338 reported observations, including 625 in the PK-guided 5-FU dosing arm and 713 in the BSA-based 5-FU dosing arm, because one study reported severe toxicity by treatment cycle rather than by patient. PK-guided dosing was associated with lower severe or grade ≥ 3 toxicity (RR 0.50, 95% CI 0.33-0.76; P = 0.001; I²=79%). PK-guided dosing was also associated with a higher objective response rate (RR 1.50, 95% CI 1.24-1.80; P < 0.0001) and disease control rate (RR 1.18, 95% CI 1.07-1.30; P = 0.001). Severe diarrhea was reduced (RR 0.33, 95% CI 0.18-0.62; P = 0.0006), whereas mucositis, neutropenia/leukopenia, and hand-foot syndrome were not significantly different between dosing strategies. CONCLUSION: PK-guided 5-FU dosing was associated with lower severe toxicity and diarrhea and higher objective response and disease-control rates than conventional BSA-based dosing. However, the evidence was derived from a small and clinically heterogeneous group of studies, and progression-free or overall-survival benefits could not be established. The findings apply predominantly to metastatic colorectal cancer treated with infusional 5-FU within FOLFOX- or FOLFIRI-based regimens. CLINICAL TRIAL REGISTRATION: Not applicable. This study was a systematic review and metaanalysis, and not a clinical trial.

Humans↗

PubMed2026

Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000 mg for 12 weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p ≥ 0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400 mg (-2.6 kg), 600 mg (-1.2 kg), and 1,000 mg groups (-3.1 kg). Compared with placebo, the 1,000 mg dose resulted in the largest reductions in body weight (mean difference, -2.30 kg; p = 0.01) and BMI (mean difference, -0.85 kg/m2; p = 0.02). The 1,000 mg dose showed preliminary efficacy for reducing body weight and BMI over 12 weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed2026

Effects of Blood Flow Restriction Training at Different Levels of Arterial Occlusion Pressure on Body Composition and Athletic Performance in Youth Soccer Players: A Randomized Controlled Trial.

This study aimed to investigate the effects of low-load blood flow restriction training (BFRT) performed at different levels of arterial occlusion pressure (AOP) on body composition, maximal strength, and athletic performance in youth soccer players. Twenty-four male youth soccer players were randomly assigned to 40% AOP group, 60% AOP group, or control group. Participants in the BFRT groups performed lower-limb resistance training at 30% of one-repetition maximum (1RM) under the corresponding pressure conditions, whereas the control group trained without BFR. Training was conducted three times per week for six weeks. Body composition, back squat 1RM, countermovement jump (CMJ), T-test, and 30-m sprint performance were assessed before and after the intervention. Results showed that lower-limb muscle mass increased significantly in both the 40% AOP group (mean change = 0.55 kg, 95% CI: 0.13 to 0.97 kg, P = 0.010) and the 60% AOP group (mean change = 0.83 kg, 95% CI: 0.37 to 1.29 kg, P < 0.001), with the 60% AOP group showing significantly greater gains than the control group (between-group difference = 1.48 kg, 95% CI: 0.40 to 2.56 kg, P = 0.008). Back squat 1RM improved significantly in both the 40% AOP group (mean change = 6.50 kg, 95% CI: 3.90 to 9.10 kg, P < 0.001) and the 60% AOP group (mean change = 9.25 kg, 95% CI: 6.75 to 11.75 kg, P < 0.001), with the 60% AOP group demonstrating superior strength gains compared with the 40% AOP group (between-group difference = 2.94 kg, 95% CI: 0.20 to 5.68 kg, P = 0.048). CMJ height and T-test performance improved significantly in both the 40% AOP group (CMJ: mean change = 2.07 cm, 95% CI: 0.80 to 3.34 cm, P = 0.002; T-test: mean change = -0.23 s, 95% CI: -0.35 to -0.11 s, P = 0.001) and the 60% AOP group (CMJ: mean change = 2.65 cm, 95% CI: 1.00 to 4.30 cm, P = 0.003; T-test: mean change = -0.26 s, 95% CI: -0.38 to -0.14 s, P < 0.001), with no significant differences between the two BFRT groups (all P > 0.05). No significant changes were observed in 30-m sprint performance across groups (all P > 0.05). This study showed that six weeks of low-load (30% 1RM) blood flow restriction training performed at both 40% and 60% AOP was associated with improvements in lower-limb muscle mass, squat strength, and selected aspects of athletic performance in youth soccer players, compared with low-load training without BFR. While both pressure levels elicited comparable improvements in CMJ and agility performance, training at 60% AOP was associated with greater adaptations in lower-limb muscle mass and squat strength, with no additional benefits observed for 30-m sprint performance.

Humans↗

PubMed2026

Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.

BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12 months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12 months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9 months of clopidogrel plus placebo versus clopidogrel plus aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.

Aged↗

PubMed2026

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate ≥ 90; 60-< 90; 30-< 60; < 30 mL/min/1.73 m2) and liver (total bilirubin ≤ 21 μmol/L or aspartate aminotransferase [AST] ≤ 31/≤ 37 [female/male] U/L; total bilirubin > 21 μmol/L or AST > 31/> 37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p > 0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c < 7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p < 0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p < 0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans↗

PubMed2026

Randomized controlled trial comparing 7-day fexuprazan-based and 14-day rabeprazole-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Fexuprazan is a newly developed potassium-competitive acid blocker used for the treatment of acid-related gastrointestinal diseases; however, clinical data regarding its efficacy in Helicobacter pylori eradication are lacking. This study evaluated the efficacy and safety of a 7-day fexuprazan-based triple therapy regimen compared with a 14-day rabeprazole-based triple therapy regimen for H. pylori infection in Korean patients. METHODS: A randomized controlled single-center study was conducted to compare the eradication rates between 7-day fexuprazan (40 mg)-based triple therapy (with 1 g amoxicillin and clarithromycin 500 mg administered twice daily) and 14-day rabeprazole (20 mg)-based triple therapy for H. pylori eradication. The primary endpoint was the success rate of H. pylori eradication, determined using the 13C-urea breath test. Safety outcomes were also evaluated. RESULTS: A total of 79 patients were randomly assigned to the fexuprazan and rabeprazole groups. In the full analysis set, eradication rates were 80.00% (32/40) in the fexuprazan group and 82.05% (32/39) in the rabeprazole group. In the per-protocol set, eradication rates were 83.78% (31/37) and 88.89% (32/36), respectively (P = 1.000 and P =.737). The overall incidence of treatment-emergent adverse events was 70.00% (28/40) in the fexuprazan group and 66.67% (26/39) in the rabeprazole group, with no significant difference between groups (P =.812); both regimens were well tolerated. Among patients with clarithromycin-susceptible strains in full analysis set, eradication rates were 93.10% (27/29) in the fexuprazan group and 87.09% (27/31) in the rabeprazole group (P =.672). In the per-protocol set, eradication rates for susceptible strains were 96.42% (27/28) in the fexuprazan group and 93.10% (27/29) in the rabeprazole group (P = 1.000). CONCLUSION: Seven-day fexuprazan-based triple therapy demonstrated eradication efficacy comparable with that of 14-day rabeprazole-based therapy in treatment-naïve Korean patients with H. pylori infection. The fexuprazan-based regimen showed a similar safety profile and comparable incidence of adverse events with that of the rabeprazole-based regimen.

Humans↗

PubMed2026

Clinical pharmacokinetics of afatinib: A systematic review.

BACKGROUND: Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure. METHODS: Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria. RESULTS: Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC0-24 and Cmax values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The Cmax of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The Cmax decreases 31.45% when given with pemetrexed. Both the AUC0-24 and Cmax increase in NSCLC and tumor state. The AUC0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients. CONCLUSION: This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.

Humans↗

PubMed2026

Changes in hemoglobin levels and cardiometabolic health in adults with metabolic syndrome - a secondary outcome analysis of a six-month randomized controlled trial.

BACKGROUND: Lower hemoglobin (Hb) levels within the normal range have been associated with favorable metabolic traits in cross-sectional studies. This study investigated whether changes in Hb levels correlated with changes in physiological and cardiometabolic parameters during a six-month behavioral intervention in individuals with metabolic syndrome. METHODS: The six-month randomized controlled trial aimed to reduce sedentary behavior in adults with metabolic syndrome (n = 64). Key measurements included fasting blood samples, insulin sensitivity during a hyperinsulinemic-euglycemic clamp, insulin-stimulated liver glucose uptake, liver fat content (LFC), indirect calorimetry, cardiorespiratory fitness, and cardiac function. Correlations between changes in these variables and changes in Hb levels at baseline, three, and six months were examined. RESULTS: Cross-sectionally, higher Hb levels correlated with lower insulin sensitivity (r=-0.35, p = 0.005), higher resting O2 consumption (r = 0.41, p < 0.001), higher resting energy expenditure (r = 0.49, p < 0.001), higher LFC (r = 0.40, p = 0.011), and greater left ventricular wall thickness (r = 0.42, p = 0.001). The intervention did not significantly impact Hb levels, and changes in Hb levels did not correlate with most cardiometabolic changes. However, reduced Hb levels correlated with reduced fasting blood glucose (r = 0.29, p = 0.032), improved insulin sensitivity (r = -0.26, p = 0.045), and increased cardiorespiratory fitness (r = -0.29, p = 0.033). CONCLUSIONS: Changes in Hb levels did not consistently correlate with changes in cardiometabolic markers during the intervention. However, reductions in Hb levels may relate to improved insulin sensitivity and fitness. Along cross-sectional correlations, this may be clinically relevant for individuals with metabolic syndrome. Further studies are merited to clarify the role of Hb levels in this high-risk group.

Humans↗

PubMed2026

Early Analgesia for the Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to evaluate the efficacy and safety of early analgesic interventions, particularly NSAIDs versus opioids, in reducing pain and improving clinical outcomes among adults with AP. METHODS: A systematic literature search was conducted across PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ClinicalTrials.gov from database/registry inception to December 2025 to obtain relevant data. Randomized controlled trials involving adults aged 18 years or older diagnosed with AP, irrespective of the etiology and severity, who were administered analgesics (opioids, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, epidural anesthesia, local anesthesia, and paracetamol) and compared with placebo, conventional treatment, or another analgesic modality were included in this review. The primary outcome assessed was pain reduction. The secondary outcomes assessed were the need for rescue analgesia, length of hospital stay, complications (local and/or systemic), mortality, and adverse drug effects. Risk of bias was assessed using the Cochrane Risk of Bias tool 2.0. Effect estimates were pooled using a random-effects meta-analysis (DerSimonian-Laird approach), while nonpooled outcomes were summarized narratively. RESULTS: A total of 13 studies were included in the analysis. NSAIDs provided pain relief comparable to opioids, with a lower incidence of local complications (RR: 0.59, 95% CI: 0.37-0.94). No significant differences in the need for rescue analgesia (OR: 0.88, 95% CI: 0.33-2.35), length of hospital stay (MD: -2.68 d, 95% CI: -6.27 to 0.91), mortality (RR: 0.76, 95% CI: 0.19-3.05), and adverse drug effects (RR: 0.55, 95% CI: 0.17-1.76) were observed. However, the findings are limited by study bias and heterogeneity. CONCLUSION: Early analgesia with NSAIDs has efficacy and safety comparable to opioids in adults with AP, with the advantage of reducing local complications.

Humans↗

PubMed2026

Efficacy and Safety Profile of a Triple Single-Pill Combination of Valsartan/Amlodipine/Chlorthalidone in Patients with Uncontrolled Hypertension.

PURPOSE: This randomized, double-blind, multicenter Phase III study evaluated the efficacy and safety profile of a single-pill triple combination of valsartan/amlodipine/chlorthalidone (KDF1901, Valdipine Plus) compared with a dual combination of valsartan/amlodipine (KDF1901-R) in patients with essential hypertension. METHODS: Patients (n = 294) with inadequately controlled hypertension after a 4-week run-in phase with valsartan/amlodipine (80/5 mg) were randomized to receive KDF1901 (valsartan/amlodipine/chlorthalidone 160/10/25 mg, n = 147) or KDF1901-R (valsartan/amlodipine 160/10 mg, n = 147) for 8 weeks. The primary efficacy endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Secondary endpoints included changes in mean sitting diastolic blood pressure (MSDBP), BP normalization rates, and response rates. Safety profile outcomes assessed treatment-emergent adverse events (TEAEs), laboratory parameters, and serious adverse events. FINDINGS: At week 8, the KDF1901 group exhibited a significantly greater reduction in MSSBP (-22.8 ± 1.0 mmHg) compared with the dual therapy group (-16.7 ± 1.0 mmHg, P < 0.0001). Similarly, the mean MSDBP reduction was significantly greater with KDF1901 (P = 0.0006). BP normalization rates (75.9% vs 54.5%, P < .0001) and response rates (73.8% vs 51.7%, P < 0.0001) were significantly higher in the triple combination group. Overall, the incidence of TEAEs was similar between groups (24.7% vs 21.5%, P = 0.5783), with mild cases of dizziness were most commonly reported. Exploratory ad hoc analyses showed statistically greater changes in sodium, potassium, and uric acid levels with triple therapy, but clinically meaningful extreme electrolyte abnormalities were rare in both groups, and the overall laboratory profile remained acceptable. IMPLICATIONS: This trial reported that the single-pill triple combination KDF1901 significantly improved BP control compared with dual therapy without compromising tolerability. GOV IDENTIFIER: NCT07116863.

Humans↗

PubMed2026

Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on weight changes and the occurrence of adverse reactions in overweight or obese adults after drug withdrawal. METHODS: Computerized searches were conducted in evidence-based databases such as PubMed, Embase, Cochrane Library and Scopus. The search period was from the establishment of the database to December 2025. Collect randomised controlled trials (RCTs) and controlled trials on GLP-1RAs, including tirzepatide, semaglutide, liraglutide, and dulaglutide, for the treatment of overweight or obese adult patients. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias V2.0 tool provided by the Cochrane Collaboration, and meta-analysis was performed using the R programming language. RESULTS: A total of 699 studies were initially retrieved. Eventually, six studies involving 8,993 patients were included in the quantitative analysis, comprising 5,553 patients in the discontinuation group and 3,440 in the continued treatment group. The results of the meta-analysis showed that, compared with the continued treatment group, the weight difference in the discontinuation group was mean difference (MD) = 17.90%, 95% confidence interval (CI) [14.11-21.69], P < 0.0001. It can be seen that there was a significant rebound in weight after drug withdrawal, and there was statistical heterogeneity among the studies (P = 0.0082). Subgroup analysis further revealed that the weight rebound amplitude after discontinuation of tirzepatide was significantly higher than that of semaglutide. This result suggests that the differences in the mechanism of action of different GLP-1RAs may be the reason for the differences in weight changes after discontinuation. In addition, the percentage difference in body weight between after and before drug withdrawal was MD = 9.11%, 95% CI [7.91-10.30], P < 0.0001, further verifying the trend of weight rebound after drug withdrawal. The summary of adverse reaction reports analyzed and studied indicates that after drug withdrawal, the overall adverse reactions of patients decreased, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by drug withdrawal. CONCLUSION: There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.

Humans↗

PubMed2026

A versatile reversed-phase liquid chromatography charged aerosol detection method for streamlined monitoring of QS-21 content and stability in liposomal adjuvant formulations.

Identifying and quantifying an active adjuvant along with its degradants in drug formulations is essential for ensuring the safety and efficacy of the drug product. QS-21 is a potent adjuvant that is being evaluated in several clinical trials and is currently formulated in licensed vaccines that protect against shingles, malaria, and RSV. In aqueous environments, QS-21 is subject to hydrolytic degradation that is influenced by pH and temperature, resulting in the formation of a degradant known as QS-21 Hydrolyzed Product, QS-21 HP, which can occur during manufacturing and/or prolonged storage. The intact QS-21 and QS-21 HP induce distinct immune response profiles, making it critical to monitor the degradation of QS-21 in vaccine adjuvant formulations. To date, there has been a paucity of reliable assays for QS-21, its isomers, and degradant QS-21 HP in liposomal adjuvant formulations available that can be transferred seamlessly in quality control (QC) environments. Herein, we introduce a simple and QC-friendly liquid chromatography coupled to a charged aerosol detector (LC-CAD) enabled by stationary phase screening combined with in silico method development optimization. The method exploits 2.7 μm fused-core phenyl hexyl particles, ensuring its versatility in standard and ultra-high pressure LC systems. This approach demonstrates a high correlation between predicted retention time (RT) and experimental outcomes with overall ∆RT < 4%. In addition, this assay shows great linearity, precision, specificity, and accuracy to advance process development characterization of new vaccine formulations.

Liposomes↗

PubMed2026

Influencer-driven lifestyle and wellness framing of intoxicating hemp products may normalize youth cannabis use.

Hemp-derived intoxicating cannabis products (DICPs) have rapidly expanded across the U.S. marketplace and are increasingly promoted on social media platforms popular among youth. This commentary highlights emerging concerns about influencer-driven DICP promotion on Instagram, where intoxicating hemp and cannabis products are embedded within lifestyle, wellness, fitness, sobriety, harm-reduction, and entertainment narratives. In ongoing monitoring of Instagram posts from leading DICP brands, we observed influencer posts that featured young-looking creators, aspirational wellness imagery, humor, slang, fast-cut editing, mocktail-making scenes, and claims positioning DICPs as "hangover-free," safer, or substitutes for alcohol or other drug use. Such content may reduce perceived risk, increase product appeal, and normalize cannabis use, particularly when promotional posts resemble organic (non-promotional) peer-culture content rather than advertising. Existing platform guidelines and regulatory approaches may inadequately address this form of influencer marketing. Enforcement is more actionable when sponsorship is clearly disclosed; however, influencers often omit brand sponsorship disclosures entirely or use vague disclosures. The absence of a disclosure does not necessarily mean that a post is non-promotional. Platforms should develop policies and algorithm-assisted surveillance approaches that identify DICP influencer content using youth-oriented cues, lifestyle and wellness framing, brand tags or links, and unverified reduced-risk or therapeutic claims.

Humans↗

PubMed2026

Multi-Omics Genome-Wide to Explore the Formation and Development Targets for Intracranial Aneurysms.

Intracranial aneurysms (IAs) represent a significant and potentially life-threatening category of disease, and there is currently a lack of effective treatment options aimed at preventing the progression of the disease. Accordingly, this study is dedicated to exploring and identifying effective drug targets that can help in the prevention of both the formation and rupture of IAs, along with a detailed examination of the underlying potential mechanisms involved in these processes. The data related to IAs for this research was obtained from the ISGC Biobank and UK Biobank. Then, we investigated the possible biological functions and unintended consequences of targeting the specific genes that were highlighted in IAs by using mediation analysis, virtual knockout experiments, and PW-MR studies. A total of 5 unique potential drug targets for IAs (FKTN, MAP3K1, PSMA4, SLC22A4, ADAM17), 4 unique potential drug targets for SAH (PSMA4, ADAM17, GPR160, SLC22A4), and 2 unique potential drug targets for UIA (SLC22A4, PRCP) were identified across brain or blood samples. Among the various candidates identified, SLC22A4 has emerged as a promising potential drug target, showing significant expression levels in both blood and brain tissues. Additionally, phenome-wide MR of SLC22A4 across 32 selected phenotypes did not identify statistically significant adverse associations after FDR correction. Virtual knockout (KO) experiments on SLC22A4 revealed that SLC22A4 KO disrupted 81 genes, all of which are involved in IAs-related pathways. Besides, we recognized BRD-K85337334 as potential candidates for targeting SLC22A4. This research indicates that an increase in SLC22A4 gene expression within the blood or brain is directly linked to a heightened risk of IAs rupture, which will aid in prioritizing the development of drugs for IAs.

Humans↗

PubMed2026

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's κ. Agreement was rated as strong where measures were ≥ 0.50, moderate where agreement was 0.30-0.49, and weak where < 0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

Humans↗

PubMed2026

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2 with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p < 0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43 months, p < 0.0001; 9.46 vs. 14.44 months, p = 0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans↗