Pharmacotherapy [JOURNAL]
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200 papers
Incretin-Based Therapies for the Treatment of Binge Eating-A Systematic Review.
White RT, Henriquez P, Innocent B … +2 more , Bullers K, Elmaoued A
Pharmacotherapy · 2026 May · PMID 41947645 · Publisher ↗
INTRODUCTION: Binge eating disorder (BED) is a common psychiatric condition associated with psychological and cardiometabolic morbidity. Psychotherapy remains a core treatment modality while pharmacologic agents such as...
INTRODUCTION: Binge eating disorder (BED) is a common psychiatric condition associated with psychological and cardiometabolic morbidity. Psychotherapy remains a core treatment modality while pharmacologic agents such as lisdexamfetamine, selective-serotonin reuptake inhibitors (SSRIs), and topiramate demonstrate variable efficacy and tolerability. Incretin therapies-specifically glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA-originally developed for type 2 diabetes mellitus (T2DM) and obesity, are an emerging therapy of interest for BED due to their effects on satiety, appetite regulation, and reward-driven eating. This systematic review examines current data surrounding the efficacy of incretin therapies in treating BED and discusses potential mechanisms underlying their effects. METHODS: This systematic review was registered with PROSPERO (CRD42024615851) and conducted in accordance with PRISMA 2020 guidelines. Comprehensive searches were performed across MEDLINE, Embase, PsycINFO, Scopus, and Cochrane CENTRAL from inception to December 2024. Eligible studies included human trials evaluating GLP-1 RAs or dual GLP-1/GIP agonists in patients with diagnosed BED or binge eating behaviors. Data were extracted on study design, interventions, eating disorder outcomes, psychiatric symptoms, weight, and cardiometabolic measures. RESULTS: Of 1125 screened records, 12 studies met inclusion criteria. Interventions studied included liraglutide, semaglutide, and dulaglutide, with sample sizes generally < 75 participants. Despite heterogeneity in study design and outcome measures, consistent reductions in binge eating behaviors were observed, reflected by improvements in Binge Eating Scale scores, reductions in binge frequency, and remission rates. GLP-1 RAs were also associated with significant reductions in body weight (-3 to -24 kg), BMI, and improvements in glycemic control among individuals with diabetes. Adverse effects were primarily gastrointestinal, with no new psychiatric safety concerns identified. DISCUSSION: GLP-1 RAs may offer dual therapeutic benefits for BED, reducing binge eating behaviors while addressing comorbid obesity and metabolic consequences. However, available evidence is limited by small sample sizes, heterogeneous methods, and short follow-up durations. Larger randomized controlled trials using standardized diagnostic criteria and validated psychiatric measures are warranted.
SGLT2 Inhibitors and GLP-1 Receptor Agonists After Acute Kidney Injury: A Systematic Review With Meta-Analysis.
Barreto EF, Garcia-Nieves YA, Johnson EC … +10 more , Eder TH, Gerberi DJ, Kashani KB, Kattah AG, Liu KD, May HP, McCoy RG, Murphy DP, Rule AD, Wieruszewski PM
Pharmacotherapy · 2026 May · PMID 41947629 · Publisher ↗
Sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are nephroprotective and their use is recommended for adults with chronic kidney disease (CKD). The role of SG...
Sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are nephroprotective and their use is recommended for adults with chronic kidney disease (CKD). The role of SGLT2i and GLP-1 RAs in patients with acute kidney injury (AKI) is unknown. This systematic review aimed to estimate the effect of SGLT2i or GLP-1 RAs on clinical outcomes in AKI. We systematically searched Embase, MEDLINE, Scopus, Web of Science Core Collection, and clinical trials registries for observational studies and clinical trials from database inception to July 3, 2025. Included studies evaluated adults (≥ 18 years) with AKI during a hospitalization and compared patients subsequently exposed to either SGLT2i or GLP-1 RAs to a non-exposed control group. Random effects meta-analyses were performed. Six studies related to SGLT2i (five observational, one randomized trial) and one related to GLP-1 RAs (one observational) met eligibility criteria (N = 432,048 patients). SGLT2i/GLP-1 RA exposure was associated with lower odds of major adverse kidney events (MAKE) (OR 0.63, 95% CI 0.46-0.86) and all-cause mortality [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.21-0.62] compared to controls. The odds for kidney replacement therapy were lower with SGLT2i therapy in the three studies where it was evaluated (OR 0.61, 95% CI 0.40-0.93). Sensitivity analyses restricted to SGLT2i data were consistent with the overall findings [MAKE OR 0.63 (95% CI 0.42-0.95); Mortality OR 0.34 (95% CI 0.18, 0.65)]. Exposure to SGLT2i or GLP-1 RAs after AKI, examined primarily in observational studies, was associated with improved clinical outcomes. These findings are promising and warrant evaluation in randomized clinical trials.
Exploring the Rabbit Holes of Pharmacotherapy.
DeVane CL
Pharmacotherapy · 2026 May · PMID 41947621 · Publisher ↗
Abstract loading — click title to view on PubMed.
Beyond Monotherapy: The Superior Efficacy of Combined GLP-1 Receptor Agonist and SGLT2 Inhibitors on Renal Biomarkers: A Systematic Review and Meta-Analysis.
AbdelMagid AM, Kamel AM, Farid SF
Pharmacotherapy · 2026 May · PMID 41947610 · Publisher ↗
Diabetic kidney disease (DKD) is a leading cause of chronic and end-stage renal diseases. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer renoprotection...
Diabetic kidney disease (DKD) is a leading cause of chronic and end-stage renal diseases. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer renoprotection; however, emerging evidence suggests that combination therapy has synergistic benefits. This meta-analysis evaluated dual versus monotherapy, focusing on the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. PubMed, Scopus, Embase, CINAHL, Medline, and Web of Science were searched until August 2025 for RCTs comparing GLP-1RA plus SGLT2i versus monotherapy or placebo in adults with T2D. The primary outcome was the change in UACR, and the secondary outcome was eGFR. Pooled standardized mean differences (SMD) were estimated using random-effects models, including subgroup and sensitivity analyses. Eight RCTs (n = 1974; sample size, 41-4000; follow-up, 16 weeks-3.4 years) were included. Combination therapy was well tolerated and significantly reduced UACR compared with monotherapy (SMD -0.25, 95% confidence interval (CI) -0.38, -0.13; I = 0%). The benefits remained significant against SGLT2i alone (SMD, -0.28) but not for GLP-1RA alone. For eGFR, dual therapy provided a modest benefit versus SGLT2i (SMD 0.12, 95% CI 0.00-0.23) but not for GLP-1RA. The effects were consistent in patients with DKD and in larger trials. Early SGLT2is and GLP-1RA combination therapy is safe and provides superior renoprotection compared to monotherapy in patients with type 2 diabetes, albuminuria, and high cardiorenal risk. Broader adoption of combination therapy could improve outcomes, although cost and access barriers remain an issue.
Treatment Adherence to Oral Direct-Acting Antiviral Agents in Hepatitis C Infection.
Khalid J, Li J, Aparasu RR
Pharmacotherapy · 2026 May · PMID 41947600 · Publisher ↗
BACKGROUND: Optimal adherence to second-generation direct-acting antiviral agents (DAAs) is crucial for preventing disease progression and reducing treatment resistance in patients with Hepatitis C virus (HCV). Therefore...
BACKGROUND: Optimal adherence to second-generation direct-acting antiviral agents (DAAs) is crucial for preventing disease progression and reducing treatment resistance in patients with Hepatitis C virus (HCV). Therefore, we examined DAA adherence and its predictors in patients with HCV. STUDY DESIGN: Retrospective cohort study. METHODS: The study cohort included adult patients with HCV in the Merative MarketScan databases from 2017 to 2019. Incident DAA users were selected with a 12-month baseline continuous enrollment. Adherence was assessed during the 8- to 24-week follow-up period, as per guidelines, using two adherence metrics: the proportion of days covered (PDC ≥ 80%) and the completion of therapy (≤ 14-day gap). Predictors of non-adherence were assessed by multivariable logistic regression based on the Andersen Behavioral Model. Sensitivity analysis was conducted at PDC ≥ 70% and ≥ 90%, and a gap of ≤ 21 days. RESULTS: Among 3412 incident DAA users, 84.79% of patients were adherent (PDC ≥ 80%), and 84.23% of patients completed the treatment without a significant gap (≥ 14 days). Several predictors were associated with non-adherence and were consistent for both adherence metrics. Older age (55-64 years, adjusted odds ratio [aOR]: 0.50, 95% Confidence Interval [CI]: 0.35-0.70) and middle-aged adults (45-54 years, aOR: 0.53, 95% CI: 0.37-0.75) were less likely to be non-adherent. High monthly out-of-pocket (OOP) costs (≥ $400) increased the risk of non-adherence (aOR: 1.25, 95% CI: 1.02-1.54). Patients with cirrhosis (compensated: aOR: 3.85, 95% CI: 2.99-4.94; decompensated: aOR: 3.02, 95% CI: 1.95-4.70), HIV infection (aOR: 1.83, 95% CI: 1.06-3.18), and substance use disorder (aOR: 1.38, 95% CI: 1.01-1.89) were found to have higher odds of being non-adherent. Patients who were prescribed the velpatasvir/sofosbuvir regimen were less likely to be non-adherent (aOR: 0.78, 95% CI: 0.62-0.99). Sensitivity analysis yields similar findings. CONCLUSIONS: Overall adherence to DAA therapy was high in HCV; however, several clinical and non-clinical factors were associated with non-adherence. Findings from this study can inform the development of targeted interventions to optimize DAA adherence in HCV.
Pharmaceutical Considerations for Oncology Risk, Screening, and Drug Dosing in the Transgender Population.
Broadwater A, Astle KN
Pharmacotherapy · 2026 Apr · PMID 41853965 · Publisher ↗
Transgender individuals make up a significant portion of the United States population, yet little data are available regarding oncologic considerations for this population. Transgender individuals may utilize gender-affi...
Transgender individuals make up a significant portion of the United States population, yet little data are available regarding oncologic considerations for this population. Transgender individuals may utilize gender-affirming hormone therapy to develop the desired secondary sex characteristics. Although there are few studies assessing hormone therapy and cancer risk in transgender individuals, available studies show no increased risk of cervical, ovarian, testicular, and prostate cancer associated with gender-affirming hormone therapy. Caution is advised when using estrogen therapy in transgender women who may be at higher risk for breast cancer due to family history or other considerations. Transgender patients should also be counseled on cancer screening recommendations depending on which tissues they have retained, even if those tissues are incongruous with their gender identity. Additionally, when providing oncologic care for transgender individuals, health care providers often utilize calculations for dosing and renal function that contain gender modifiers. Duration of hormone therapy can be utilized as a factor for determining whether to utilize gender assigned at birth or gender identity for these calculations. Through education and cultural awareness, health care providers can provide a simultaneously effective and gender-affirming medical experience to the transgender population.
Outcomes of CDK4/6 Inhibitor-Based Therapy in Premenopausal HR+/HER2- Metastatic Breast Cancer: Real World Data From A Multicenter Study.
Odabaş H, Alomari O, Orman S … +10 more , Sever N, Tuzun EK, Acarbay A, Ercin E, Aydogan M, Guren AK, Mokresh ME, Topal A, Yildirim S, Ozcelik M
Pharmacotherapy · 2026 Apr · PMID 41851603 · Publisher ↗
BACKGROUND: Breast cancer is the leading cause of cancer-related death in women worldwide. Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) represents...
BACKGROUND: Breast cancer is the leading cause of cancer-related death in women worldwide. Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) represents the most common subtype. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET) constitute standard first-line treatment, yet evidence comparing ribociclib and palbociclib in peri-/premenopausal patients remains limited. This study aimed to evaluate and compare the real-world efficacy and safety profiles of ribociclib versus palbociclib in combination with ET in this patient population. METHODS: This multicenter, retrospective study included 267 peri-/premenopausal patients with HR+/HER2- MBC treated with palbociclib (n = 86) or ribociclib (n = 181) plus ET across five centers in Turkey between 2020 and 2024. Primary end points were progression-free survival (PFS) and overall survival (OS); secondary end points included objective response rate (ORR) and safety. Survival analyses used Kaplan-Meier and Cox regression methods using R software; adverse events were graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. RESULTS: The mean age was 42.96 years. Median follow-up was 19.6 months for palbociclib and 13.3 months for ribociclib (p = 0.003). No statistically significant differences were observed between palbociclib and ribociclib in median PFS (24.05 vs. 24.41 months; HR: 1.06; p = 0.94) or OS (not reached vs. 41.03 months; p = 0.86). The ORR was comparable at 64% for palbociclib and 69% for ribociclib (p = 0.459). Safety profiles were similar; any-grade adverse events occurred in 77.9% of palbociclib and 80.7% of ribociclib patients (p = 0.600). Neutropenia was the most common toxicity (72.1% palbociclib vs. 74.0% ribociclib). Grade 3-4 adverse events occurred in 29.1% of the palbociclib group and 40.3% of the ribociclib group (p = 0.074). Subgroup analyses showed consistent treatment effects across age, visceral involvement, and line of therapy. CONCLUSION: In real-world peri-/premenopausal patients with HR+/HER2- MBC, ribociclib and palbociclib combined with ET demonstrate comparable efficacy and tolerability. These findings support flexible treatment choice based on individual patient profiles and preferences.
A Systematic Review of Clinically Significant Drug-Drug Interactions With Phenobarbital and Primidone.
Ghattas K, Liu JT, Elsamadisi P … +2 more , Morien-Medoff A, Wong A
Pharmacotherapy · 2026 Apr · PMID 41833537 · Publisher ↗
Phenobarbital (PB) is historically used for management of seizure disorders but more recently has emerged as a prominent option for the management of alcohol withdrawal syndrome given data suggesting its benefit over ben...
Phenobarbital (PB) is historically used for management of seizure disorders but more recently has emerged as a prominent option for the management of alcohol withdrawal syndrome given data suggesting its benefit over benzodiazepines. An important consideration of PB therapy is its induction of cytochrome-P 450 enzymes (CYP450), which may lead to underrecognized drug-drug interactions (DDIs). Knowledge of these PB DDIs, including their onset and offset, is important to better elucidate how to manage these DDIs. To identify published literature evaluating the relevance of DDIs between PB and selected medications, a systematic review was performed including literature published through January 2026, focused on the administration of both PB and a list of medications based on tertiary medication database review as well as clinical relevance, including anticoagulants, antimicrobials, and immunosuppressants. Included articles had to identify outcomes of interest, which were focused on laboratory, pharmacokinetic, and clinical outcomes, and had to be in humans. Data extraction included the onset and offset of PB DDIs and potential PB dose-response and magnitude of induction of target medication. A total of 3271 articles were identified, with 50 studies meeting inclusion criteria, which included both adult and pediatric populations. Thirteen studies evaluated onset of PB induction, which ranged from 6 h to 30 days. Eight studies evaluated offset of PB induction, which ranged from 2 to 8 weeks. Limited data demonstrated a PB dose-response relationship in terms of magnitude of CYP induction. We found that 86% of the included studies demonstrated an impact by PB on outcomes, which were often related to therapeutic drug monitoring. Data suggest that PB does lead to clinically significant DDIs in multiple classes of medications. Future areas of research include focused evaluations on clinical outcomes, as well as studies specifically evaluating single high-dose PB and impact on DDI outcomes.
Current State of Clinical Care of People With Cystic Fibrosis.
McKinzie CJ, Kam CW, Beringer PM … +6 more , Wright BA, Bullington WM, Garcia S, Grant JJ, Pettit RS, Young DC
Pharmacotherapy · 2026 Apr · PMID 41832906 · Publisher ↗
The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has dramatically changed the landscape of the clinical care of people with cystic fibrosis (PwCF). In particular, highly effective modul...
The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has dramatically changed the landscape of the clinical care of people with cystic fibrosis (PwCF). In particular, highly effective modulator therapy (HEMT) availability for the majority of PwCF has led to changes in pharmacotherapy regimens and clinical outcomes but has also been associated with adverse effects and drug interactions. The role of CFTR modulator therapy perinatally continues to be of great interest, related to both the mother with CF as well as the infant in utero and after birth. As the median life expectancy for PwCF continues to increase, consideration must also be given for treatment of cardiovascular disease and other comorbidities as well as cancer screening and other preventative care measures.
DILIConsult: A Multi-Agent Large Language Model Framework for Evaluating Drug-Induced Liver Injury in ICU Settings.
Ho AZT, Law JZF, Wang A … +2 more , Lim DYZ, Ong JCL
Pharmacotherapy · 2026 Apr · PMID 41826786 · Full text
BACKGROUND: Large language models (LLMs) can support clinical decision-making by parsing databases and extracting relevant information. However, evaluating drug-induced liver injury (DILI) often requires processing lengt...
BACKGROUND: Large language models (LLMs) can support clinical decision-making by parsing databases and extracting relevant information. However, evaluating drug-induced liver injury (DILI) often requires processing lengthy clinical histories alongside reference materials like LiverTox, which can exceed context lengths of conventional LLMs. Challenges such as information truncation hinder standard approaches like prompt engineering and retrieval-augmented generation (RAG). To address these limitations, this study introduces DILIConsult, an agentic LLM pipeline based on GPT-4, designed to intelligently parse clinical and drug information. METHODS: To develop DILIConsult, we compared GPT-4-Turbo versus GPT-4o for extracting DILI characteristics from LiverTox descriptions. We tested two approaches to analyzing cases of suspected DILI: full-length case analysis versus sequential drug-specific evaluations. We evaluated DILIConsult on cases of suspected DILI identified from the open source Medical Information Mart for Intensive Care-IV (MIMIC-IV) ICU dataset based on American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) criteria. Outputs from DILIConsult were compared against a panel of clinicians comprising an ICU pharmacist, an ICU junior attending physician, and an ICU resident. Responses were evaluated by two senior ICU attending physicians. RESULTS: Using GPT-4o and a sequential approach demonstrated improved performance in the extraction of DILI characteristics and analysis of suspected DILI. DILIConsult achieved the best mean rank of 1.66 ± 0.75 in knowledge recall and ranked second for reasoning (2.00 ± 0.64) and reflection of current medical consensus (2.05 ± 0.62). DILIConsult ranked last with mean ranks of 2.07 ± 0.52 and 2.09 ± 0.72 for less omission of important information and content inaccuracy, respectively. CONCLUSION: DILIConsult demonstrates the potential of LLMs to assist clinicians in evaluating DILI. The findings emphasize the importance of task division in LLM-driven workflows to minimize information loss.
Comprehensive Review of Candidozyma (Candida) auris Management: Insights From the Society of Infectious Diseases Pharmacists.
Rux CE, Johnson MD, Grant VC … +7 more , Katipunan SG, Chahine EB, Smith DJ, Lockhart SR, Drwiega E, Gubbins PO, SIDP as a corporate author
Pharmacotherapy · 2026 Apr · PMID 41821213 · Publisher ↗
Candidozyma (Candida) auris has emerged over the past two decades as a formidable global health threat due to its multidrug resistance, persistence in healthcare environments, and rapid nosocomial spread. Recently reclas...
Candidozyma (Candida) auris has emerged over the past two decades as a formidable global health threat due to its multidrug resistance, persistence in healthcare environments, and rapid nosocomial spread. Recently reclassified into the genus Candidozyma based on phylogenomic analysis, C. auris poses major challenges for both clinical management and infection control. Its ability to tolerate heat, salinity, and disinfectants supports long-term survival on surfaces and medical devices, facilitating transmission. Biofilm formation further enhances virulence and resistance to antifungal therapy. Clinical presentations range from asymptomatic colonization to invasive infections, with mortality rates approaching 50%. Echinocandins remain an important first-line treatment option, but their fungistatic activity, limited tissue penetration, and emerging resistance contribute to suboptimal outcomes, highlighting the need for new agents and optimized dosing strategies. The role of triazoles and amphotericin B is significantly limited by resistance and associated toxicities, while newer agents such as ibrexafungerp, fosmanogepix, and rezafungin show promising in vitro activity but lack substantial supporting clinical data. Combination therapy may also offer potential benefit, though supporting evidence is sparse. Infection control methods including active surveillance, contact precautions, and environmental disinfection with sporicidal agents and avoidance of ineffective quaternary ammonium compounds are key to preventing the nosocomial spread of C. auris. Despite growing awareness, effective decolonization strategies are lacking, and recurrence and transmission continue to pose challenges. Ongoing efforts to refine antifungal therapy, improve rapid diagnostics, and strengthen infection control practices are essential to mitigating the spread of this pathogen and optimizing outcomes for patients.
Response to "Comment on C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio: Can They Be Used Interchangeably in Tracking Clozapine-Related Inflammation?".
Bihelek N, Bousman CA, Honer WG … +1 more , Rafizadeh R
Pharmacotherapy · 2026 Apr · PMID 41814137 · Publisher ↗
Abstract loading — click title to view on PubMed.
Real-World Cardiovascular Outcomes of GLP-1 Receptor Agonists in Women With Type 2 Diabetes and Breast Cancer.
Cornelio CK, Cowart K, Perkins J … +5 more , Alomar ME, Gayoso RP, Miranda AC, Phan AT, White RT
Pharmacotherapy · 2026 Apr · PMID 41801847 · Publisher ↗
INTRODUCTION: The cardiovascular (CV) benefits of glucagon-like-peptide-1 receptor agonist (GLP-1 RA) therapies are not well-established in women with breast cancer and type 2 diabetes (T2D). OBJECTIVES: The primary obje...
INTRODUCTION: The cardiovascular (CV) benefits of glucagon-like-peptide-1 receptor agonist (GLP-1 RA) therapies are not well-established in women with breast cancer and type 2 diabetes (T2D). OBJECTIVES: The primary objective of this study was to compare the incidence of major adverse cardiovascular events (MACE) in women with T2D and breast cancer receiving GLP-1 RA therapy versus non-GLP-1 RA diabetes medications. METHODS: This retrospective study included women with T2D, diagnosed with breast cancer at ≥ 40 years old from December 16, 2014 to December 16, 2024 and having exposure to diabetes medications of interest (either GLP-1 RA or non-GLP-1 RA) within 5 years of these diagnoses. The primary end point, MACE, was a composite of myocardial infarction, ischemic stroke, coronary revascularization, cardiac arrest, or heart failure, within 5 years of the index date. Propensity score matching was performed. Participants were excluded from each individual outcome analysis if they had the outcome prior to the index date. Incidence rates, risk ratio (RR), 95% confidence interval (CI), and p-value were reported for each outcome. RESULTS: After matching, 19,608 patients were included in each cohort (mean age 64 years). Obesity and alkylating agents were more commonly reported in the GLP-1 RA cohort. Semaglutide was the most prescribed GLP-1 RA at index (45.1%). MACE occurred in 10.6% of the GLP-1 RA cohort and 13.4% of the non-GLP-1 cohort (RR 0.80, 95% CI 0.75-0.85, p < 0.001). Individual MACE end points, ischemic heart disease, and end-stage renal disease were significantly lower in the GLP-1 RA-treated cohort. GLP-1 RA use was also associated with a 61.6% relative risk reduction in all-cause mortality (RR 0.38, 95% CI 0.36-0.41, p < 0.001). Pancreatitis incidence was similar between groups (p = 0.057), whereas cholelithiasis was significantly lower with GLP-1 RA therapy (p < 0.001). CONCLUSIONS: This study demonstrated the potential CV benefit of GLP-1 RA therapies among a population of female breast cancer survivors with T2D. Randomized trial data are needed to confirm these findings.
Models Integrating Disease Heterogeneity and MPA Exposure Predict Systemic and Renal Efficacy of Mycophenolate in Pediatric Lupus Nephritis.
Liu B, Chen L, Lin J … +7 more , Liu X, Liu X, Huang Z, Huang M, Tang K, Jiang X, Chen P
Pharmacotherapy · 2026 Apr · PMID 41801808 · Publisher ↗
OBJECTIVES: This study aimed to develop and validate integrated prediction models for pediatric lupus nephritis (LN) treated with a mycophenolate mofetil (MMF)-based induction regimen (combined with glucocorticoids and h...
OBJECTIVES: This study aimed to develop and validate integrated prediction models for pediatric lupus nephritis (LN) treated with a mycophenolate mofetil (MMF)-based induction regimen (combined with glucocorticoids and hydroxychloroquine), incorporating both disease heterogeneity and pharmacokinetic variability. The primary model predicts the achievement of low disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2 K] ≤ 4) at 12 months, while a secondary model predicts renal complete response during the same period. METHODS: A total of 120 children with LN treated with MMF between 2001 and 2025 were included. The follow-up time from MMF initiation was 12 months. Comprehensive data encompassing clinical phenotypes, organ function, immunological profiles, and pharmacokinetic parameters were collected. We employed a data-driven approach to select key features from a comprehensive set of variables reflecting disease heterogeneity and drug exposure. Seven machine learning (ML) algorithms were evaluated, with their performance assessed using area under the curve (AUC), precision, recall, F1-score, and accuracy. For the secondary outcome of complete renal response, a separate model was constructed using seven similar ML algorithms. For the primary outcome, the incremental value of adding pharmacokinetic data was quantified using the Net Reclassification Improvement (NRI). The optimal models were further validated using calibration curves and decision curve analysis, and interpreted via SHAP analysis. RESULTS: The final integrated model for predicting low disease activity, based on a logistic regression framework, demonstrated robust performance, achieving an AUC of 0.77 in the test set, with a supporting F1-score of 0.86. The incorporation of the area under the concentration-time curve for mycophenolic acid (MPA-AUC) provided significant incremental predictive value over a clinical-only model (ΔAUC = +0.05), which was further confirmed by an NRI of 0.1309. For predicting complete renal response, a random forest model achieved an AUC of 0.88. Key variables influencing treatment response across models included MPA exposure, corticosteroid dose, immunological, renal, and hepatic parameters. Both models were well-calibrated and provided significant net benefit in decision curve analysis. CONCLUSION: We present predictive models that incorporate a comprehensive profile of disease and drug-related heterogeneity to stratify pediatric patients with LN by their likelihood of responding to MMF. This integrated approach offers a strategy to optimize initial treatment selection by directly addressing the challenge of clinical variability.
Effectiveness of Stimulant Treatment in Preventing Fractures and Head Injuries in Patients With Narcolepsy: A Self-Controlled Case Series Study.
Zheng Y, Fukasawa T, Masuda S … +3 more , Takeuchi M, Anno T, Kawakami K
Pharmacotherapy · 2026 Apr · PMID 41801771 · Publisher ↗
BACKGROUND: Previous cohort studies have investigated whether stimulants reduce injury risk in narcolepsy, but they faced potential biases such as confounding by indication and immortal time bias. We conducted a self-con...
BACKGROUND: Previous cohort studies have investigated whether stimulants reduce injury risk in narcolepsy, but they faced potential biases such as confounding by indication and immortal time bias. We conducted a self-controlled case series study to address these biases and assess the effect of stimulant use on the risk of fracture and head injury in patients with narcolepsy. METHODS: We used a Japanese health insurance claims database to identify patients with narcolepsy who were newly exposed to stimulants and who experienced fracture or head injury. We then applied multivariable conditional Poisson regression models to estimate adjusted incidence rate ratios (aIRRs) and their 95% confidence intervals (CIs) for outcomes, comparing the focal window with the referent window. Subgroup analyses assessed individual stimulants (methylphenidate, modafinil, and pemoline). RESULTS: Among 1790 new stimulant users, 233 had fracture and 189 had head injury. Overall stimulant use was not associated with fracture (aIRR, 0.89; 95% CI, 0.57-1.39) or head injury (aIRR, 1.40; 95% CI, 0.87-2.25). In subgroup analyses, methylphenidate use was associated with a lower fracture risk (aIRR, 0.28; 95% CI, 0.08-0.94) but did not affect head injury (aIRR, 1.16; 95% CI, 0.34-3.92). We observed no association between modafinil or pemoline and either outcome. CONCLUSION: Our results indicate that overall stimulant use did not decrease the risk of fracture or head injury in patients with narcolepsy. However, methylphenidate may help prevent fractures. Clinicians should balance the safety and effectiveness of each stimulant with additional preventive strategies for injury.
Safety and Efficacy of Recaticimab in Dyslipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Abdeldayem MR, Elsherbeeny A
Pharmacotherapy · 2026 Apr · PMID 41801769 · Publisher ↗
Dyslipidemia is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). Recaticimab is a novel humanized monoclonal antibody that specifically targets proprotein convertase subtilisin/kexin type 9...
Dyslipidemia is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). Recaticimab is a novel humanized monoclonal antibody that specifically targets proprotein convertase subtilisin/kexin type 9 (PCSK9). It has shown promising results in reducing low-density lipoprotein cholesterol (LDL-C) levels. Here, we aim to further investigate the safety and efficacy of recaticimab in patients with dyslipidemia. We comprehensively searched PubMed, Scopus, Web of Science, and Cochrane Library databases to identify all randomized controlled trials (RCTs) comparing recaticimab with placebo. Eligible RCTs were selected, and their data were extracted and analyzed using the RevMan software. Four studies involving 1657 patients were included in this meta-analysis. In terms of efficacy outcomes, compared with the placebo group, recaticimab significantly decreased levels of LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), triglyceride (TG), and lipoprotein(a) [Lp(a)], with the following values, respectively: (mean difference (MD): -52.62, 95% confidence interval (CI) [-57.25, -47.99], p < 0.00001); (MD: -47.03, 95% CI [-48.96, -45.11], p < 0.00001); (MD: -44.33, 95% CI [-46.08, -42.58], p < 0.00001); (MD: -8.83, 95% CI [-13.03, -4.63], p < 0.0001); and (MD: -29.21, 95% CI [-32.10, -26.31], p < 0.00001). In terms of safety outcomes, there was no significant difference between recaticimab and placebo groups in the incidence of any adverse events (odds ratio (OR): 1.16, 95% CI [0.90, 1.51], p = 0.26), serious adverse events, upper respiratory tract infections, or elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT). However, recaticimab was associated with higher odds of injection site reactions compared with placebo (OR: 2.65, 95% CI [1.24, 5.67], p = 0.01). Recaticimab significantly reduced LDL-C levels and was associated with a manageable safety profile, even with dosing intervals of up to 12 weeks. Further studies should be conducted globally in larger and more diverse patient populations.
Comment on "C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio: Can They Be Used Interchangeably in Tracking Clozapine-Related Inflammation?".
Kikuchi Y
Pharmacotherapy · 2026 Apr · PMID 41800824 · Publisher ↗
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The Effect of Losartan in Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer: A Randomized, Controlled Study.
Mahmoud AMAS, Shash E, Ateyya H … +2 more , Okasha FA, El Said NO
Pharmacotherapy · 2026 Apr · PMID 41800821 · Publisher ↗
BACKGROUND: Paclitaxel-induced peripheral neuropathy (PIPN) is a condition that persists chronically in more than 60% of affected individuals, and currently there are no proven PIPN prophylaxis. Pre-clinical data suggest...
BACKGROUND: Paclitaxel-induced peripheral neuropathy (PIPN) is a condition that persists chronically in more than 60% of affected individuals, and currently there are no proven PIPN prophylaxis. Pre-clinical data suggest the angiotensin-II-receptor blocker losartan may attenuate neuro-inflammation and nerve injury. This study was conducted to assess losartan's neuroprotective effect against PIPN in patients with breast cancer. METHODS: In this single-center, open-label, randomized, controlled trial, women with early-stage breast cancer scheduled for weekly paclitaxel (80 mg/mg or 12 doses) were enrolled and randomized 1:1 to losartan 100 mg once daily plus standard care or standard care alone. The primary end point was incidence of grade 2 or higher neuropathy, per National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE v5.0). Secondary end points included time-to-neuropathy (in days), patient quality of life (QoL) assessed by Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX), pain intensity using visual-analogue scale (VAS), serum nerve growth factor (NGF) levels, and safety. RESULTS: Between December 2023 and December 2024, 89 Patients Were Randomized (Losartan, n = 45; Control, n = 44). Losartan Significantly Reduced Grade ≥ 2 Neuropathy Incidence (33.3% vs. 86.4%, p < 0.001) and Delayed Its Onset (73.27 vs. 43.75 Days; Hazards Ratio [HR] = 0.2, 95% Confidence Interval [CI]: 0.11-0.35) Compared With Standard Care Alone, Respectively. At 12 Weeks, Patients Treated With Losartan Reported Superior QoL (FACT/GOG-NTX: 31.87 ± 6.43 vs. 15.45 ± 10.04; p < 0.001) and Reduced Pain Scores (Median VAS 3 vs. 8; p < 0.001) Compared With Standard Care Alone, Respectively. NGF Levels Were Comparable and Adverse Events Were Similar Between Groups. CONCLUSIONS: Daily losartan reduced and delayed clinically significant paclitaxel-induced neuropathy while improving patient-reported outcomes, without additional toxicity. These findings support repurposing losartan as a low-cost PIPN prophylactic and justify validation in larger, multicenter trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06135493).
Impact of Glucagon-Like Peptide-1 Receptor Agonists on Proteinuria in Kidney Transplant Recipients.
Shabanowitz S, Clark R, Allen RB … +2 more , Chandran M, Yang A
Pharmacotherapy · 2026 Apr · PMID 41800749 · Publisher ↗
INTRODUCTION: Proteinuria is a marker of kidney dysfunction and increased cardiovascular mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown significant cardiorenal benefits in chronic kidney dise...
INTRODUCTION: Proteinuria is a marker of kidney dysfunction and increased cardiovascular mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown significant cardiorenal benefits in chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). However, the impact of GLP-1 RAs on cardiorenal outcomes in kidney transplant recipients (KTRs) remains unclear. This study aims to assess the effect of GLP-1 RA therapy on proteinuria and metabolic parameters in KTRs, with and without T2DM, 12 months following GLP-1 RA initiation. METHODS: A single-center, retrospective study was conducted to evaluate the safety and efficacy of GLP-1 RAs in adult KTRs from June 1, 2022 to December 31, 2023. Primary outcomes were changes in urine protein-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) at 1, 3, 6, and 12 months after initiation of GLP-1 RAs. Secondary outcomes assessed changes in estimated glomerular filtration (eGFR), body mass index (BMI), and hemoglobin A1c (A1C). Safety outcomes included cardiovascular hospitalizations, acute kidney injury, pancreatitis, and biopsy-proven rejection within 12 months. RESULTS: Forty KTRs received GLP-1 RA therapy with a mean time to initiation of 4.3 months post-transplant, and the majority of patients had T2DM (87.5%). Baseline UPCR and UACR were 0.86 and 669 mg/g, respectively. UPCR at 1, 3, and 6 months post-initiation was 0.38 g/g, 0.37 g/g, and 0.30 g/g, respectively. UACR at 1, 3, and 6 months post-initiation was 313 mg/g, 285 mg/g, and 234 mg/g, respectively. A 55% decrease from baseline in UPCR and UACR was observed at 1 month (p = 0.070) and a 50% decrease from baseline was observed at 12 months (p = 0.058), achieving UPCR of 0.43 g/g and UACR of 320 mg/g. A1C, eGFR, and BMI remained stable. Minimal safety events occurred. CONCLUSION: GLP-1 RAs demonstrated clinically significant improvements in proteinuria as early as 1 month post-initiation in KTRs. Proteinuria significantly improved from severely increased to moderately increased at 6 months following GLP-1 RAs, with good tolerability. GLP-1 RAs may offer renal benefits in KTRs with T2DM without compromising allograft function. Future studies should include closer monitoring of KTRs on immunosuppression with high gastrointestinal adverse effect profiles, and larger studies are needed to assess the long-term impact of GLP-1 RAs in KTRs irrespective of T2DM.
Maternal and Pediatric Precision in Therapeutic Knowledge Portal (MPRINT-KP): Landscape Analysis of Pharmacology Research in Maternal and Pediatric Patient Populations.
Liu X, Shendre A, Wang L … +30 more , O'Kane A, Ma H, Chiang CW, Zaidi SS, Aboshady OA, So G, Tillman EM, Kirkpatrick LM, Costantine M, Grannis S, Rogerson CM, Bartlett C, Rahurkar S, Cheng L, Ouyang J, Wei P, Zhu Z, Li S, Huang Y, Wang L, Cao W, Jiang H, Liu J, Oteng SR, Goodwin A, Deypalubos JAF, Zhang S, Bies R, Quinney SK, Li L
Pharmacotherapy · 2026 Mar · PMID 41730795 · Full text
Pregnant women and children have been underrepresented in clinical studies due to ethical concerns and perceived vulnerabilities. This resulted in a significant gap in knowledge regarding the safety and efficacy of medic...
Pregnant women and children have been underrepresented in clinical studies due to ethical concerns and perceived vulnerabilities. This resulted in a significant gap in knowledge regarding the safety and efficacy of medications for these populations. Maternal and Pediatric PRecision In Therapeutics Knowledge Portal (MPRINT-KP) is designed to provide a comprehensive view of pharmacokinetic, pharmaco-epidemiology, and clinical trial research evidence in maternal and pediatric patient populations. MPRINT-KP Silver was generated upon BioBERT models, due to their supreme performance in classifying pharmacokinetic, pharmaco-epidemiology, and clinical trial papers from PubMed, with an F1-score > 0.91. As of April 1, 2025, MPRINT-KP Silver contains 758,560 clinical pharmacology research papers in maternal and pediatric populations. The landscape analysis revealed a large number of drugs with pharmacology knowledge gaps, which is calculated as the relative frequency of drugs with no or weak (i.e., less than five publications) evidence in each of pharmacokinetic, pharmaco-epidemiology, or clinical trial study type. The highest pharmacotherapy knowledge gaps are in postpartum women, pregnant women, and pediatric patients between 0-12 and 12-18 years of age (51.37%, 32.47%, 25.82%, 32.11%, respectively). Pharmacovigilance analyses were conducted on highly prescribed drugs with limited pharmacology evidence in pediatric patients 0-2 year old and pregnant women using United States Food and Drug Administration Adverse Event Reporting System (FAERS) and MarketScan claims data. A number of new drug-associated adverse drug events (ADEs) were discovered. In pediatric patients, there were crisaborole-associated hemorrhage and moxifloxacin-associated cardiac toxicities. In pregnant women, the analysis revealed terconazole-associated abnormalities of heartbeat; benzonatate-associated depressive and anxiety disorders; buspirone-associated abnormalities of heartbeat; cyclobenzaprine-associated tubulo-interstitial nephritis; and pantoprazole-associated hearing loss and voice and resonance disorders. For the first time, a large-scale landscape analysis of pharmacotherapy knowledge gap in both maternal and pediatric patient populations was conducted and identified new drug associated ADE evidence using real world data.
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