Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. RESULTS: Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. CONCLUSIONS: The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.

Vonoprazan With Amoxicillin or Amoxicillin and Clarithromycin for the Treatment of Helicobacter pylori Infection.

OBJECTIVES: To describe the pharmacology, efficacy, safety, and potential role of vonoprazan with amoxicillin or amoxicillin and clarithromycin for the treatment of Helicobacter pylori infection in adults. DATA SOURCES: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched using the terms: (vonoprazan OR voquezna) AND ("H. pylori" OR "Helicobacter pylori") AND amoxicillin with no date limitations up to November 3, 2022. STUDY SELECTION AND DATA EXTRACTION: Studies assessing the efficacy and safety of vonoprazan with amoxicillin and/or clarithromycin were included and divided into 3 groups based on different comparisons between treatment regimens used in each group. DATA SYNTHESIS: Ten clinical trials and 17 observational studies were included. Vonoprazan-based therapy demonstrated greater acid inhibition and similar or higher efficacy than proton-pump inhibitor (PPI)-based therapy in treatment-naïve patients and with clarithromycin-resistant infections. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Proton-pump inhibitor-based therapies have not reached the desired successful eradication rate of 90% for H. pylori infection. Vonoprazan-based therapies being at least as effective as PPI-based therapies offer an alternative for patients with H. pylori infection. CONCLUSION: Vonoprazan-based therapies were effective and well tolerated for the treatment of H. pylori infection in adults. These regimens provide an important alternative with prolonged acid inhibition, lower potential for CYP2C19 polymorphism, and at least comparable efficacy and safety versus PPI-based therapies in patients with H. pylori infections. Thus, vonoprazan-based therapy should be considered for certain patients, for example, those with failure to PPI-based treatments.

Gaps in Evidence-based Treatment of Concurrent Attention Deficit Hyperactivity Disorder and Opioid Use Disorder: A Scoping Review.

OBJECTIVES: To describe the effectiveness of medications for the treatment of opioid use disorder (OUD) and attention deficit/hyperactivity disorder (ADHD). DATA SOURCES: Literature search of PubMed, Embase, Web of Science, CINAHL, Medline, PsycINFO, and Google Scholar was performed for studies published from inception to October 25, 2022. STUDY SELECTION AND DATA EXTRACTION: Studies were included if patients were diagnosed with OUD and ADHD and had pharmacotherapy for either condition. Abstracts, commentaries, reviews, case reports, case series, non-English articles, and animal studies were omitted. DATA SYNTHESIS: This review found 18 studies. Treatment of ADHD was evaluated for impact on ADHD and OUD outcomes, while treatment of OUD was evaluated for OUD-related outcomes. Outcomes assessed included markers for symptom intensity, adherence, and treatment failure. While results were mixed, treatment of ADHD was largely associated with improvements in ADHD severity and retention in OUD treatment programs. ADHD severity was associated with higher rates of illicit substance abuse and worse OUD-related outcomes. It could not be determined which medications for treatment of OUD should be prioritized. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review summarized key findings from studies that treated ADHD or OUD among dually diagnosed patients and highlighted methodological considerations for future research. CONCLUSIONS: Treatment of ADHD is warranted among patients with OUD and ADHD to improve retention in OUD treatment programs and reduce illicit substance abuse. Pharmacotherapy for the treatment of ADHD or OUD should continue to be determined based on patients' characteristics and the capabilities of the treatment program.

Medication adherence in Medicare-enrolled older adults with asthma before and during the coronavirus disease 2019 pandemic.

BACKGROUND: Data regarding medication adherence in older adults with asthma before and during the coronavirus disease 2019 (COVID-19) pandemic are lacking. OBJECTIVE: To evaluate medication adherence and determine factors associated with adherence in Medicare-enrolled older adults with asthma before and during the COVID-19 pandemic. METHODS: This was a retrospective cohort analysis of Medicare-enrolled patients with asthma. Medication adherence was measured using rates of proportion of days covered for dates January to July 2019 and January to July 2020. Patients less than 65 years of age, with chronic obstructive pulmonary disease, or with cystic fibrosis were excluded. Paired t tests assessed change in adherence between 2019 and 2020. Logistic regression evaluated association of age, sex, depression, moderate or severe asthma, use of a 90-day supply, having 3 or more albuterol fills, number of medications, medication-related problems, prescribers, pharmacies, controller medication classes, and systemic corticosteroid fills with high adherence (proportion of days covered ≥ 80%). RESULTS: Mean adherence to asthma controller medications ranged from 75% to 90%, in 2019. Adherence significantly decreased (P < .001) from 51% to 70% for all controller medications, except theophylline in 2020. Similar results were observed among patients with moderate or severe asthma. In 2019 and 2020, number of controller medications, 3 or more albuterol fills, and having a 90-day supply were associated with high adherence (P < .001). CONCLUSION: Adherence to asthma controller medications decreased considerably during the COVID-19 pandemic among Medicare-enrolled patients with asthma. Patients with markers for more severe asthma, overuse of albuterol, and a 90-day supply of controller medications were more likely to have high adherence. These findings can be used to identify opportunities to improve adherence and prescribing among adult patients with asthma.

Evidence Needed for Efficacy of Antidepressant Medications Among Patients With Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) experience pain from inflammation, joint destruction, and neuropathy. Antidepressants may play a role among patients with RA and depression, fibromyalgia, or neuropathy to achieve desired outcomes. This commentary evaluated evidence for medications individually and identified important variables for future research. While we await the results of well-designed studies, a trial of duloxetine or milnacipran may be considered for patients with remnant pain and RA remission. Research is needed to evaluate the efficacy and safety of serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants in patients with RA and associated comorbid conditions.

Potentially Inappropriately Prescribed Medications Among Medicare Medication Therapy Management Eligible Patients with Chronic Kidney Disease: an Observational Analysis.

BACKGROUND: Potentially inappropriately prescribed medications (PIPMs) among patients with chronic kidney disease (CKD) may vary among clinical settings. Rates of PIPM are unknown among Medicare-enrolled Medication Therapy Management (MTM) eligible patients. OBJECTIVES: Determine prevalence of PIPM among patients with CKD and evaluate characteristics of patients and providers associated with PIPM. DESIGN: An observational cross-sectional investigation of a Medicare insurance plan for the year 2018. PATIENTS: Medicare-enrolled MTM eligible patients with stage 3-5 CKD. MAIN MEASURES: PIPM was identified utilizing a tertiary database. Logistic regression assessed relationship between patient characteristics and PIPM. KEY RESULTS: Investigation included 3624 CKD patients: 2856 (79%), 548 (15%), and 220 (6%) patients with stage 3, 4, and 5 CKD, respectively. Among patients with stage 3, stage 4, and stage 5 CKD, 618, 430, and 151 were with at least one PIPM, respectively. Logistic regression revealed patients with stage 4 or 5 CKD had 7-14 times the odds of having a PIPM in comparison to patients with stage 3 disease (p < 0.001). Regression also found PIPM was associated with increasing number of years qualified for MTM (odds ratio (OR) 1.46-1.74, p ≤ 0.005), female gender (OR 1.25, p = 0.008), and increasing polypharmacy (OR 1.30-1.57, p ≤ 0.01). Approximately 14% of all medications (2879/21093) were considered PIPM. Majority of PIPMs (62%) were prescribed by physician primary care providers (PCPs). Medications with the greatest percentage of PIPM were spironolactone, canagliflozin, sitagliptin, levetiracetam, alendronate, pregabalin, pravastatin, fenofibrate, metformin, gabapentin, famotidine, celecoxib, naproxen, meloxicam, rosuvastatin, diclofenac, and ibuprofen. CONCLUSION: Over one-third of Medicare MTM eligible patients with CKD presented with at least one PIPM. Worsening renal function, length of MTM eligibility, female gender, and polypharmacy were associated with having PIPM. Majority of PIPMs were prescribed by PCPs. Clinical decision support tools may be considered to potentially reduce PIPM among Medicare MTM-enrolled patients with CKD.

Impact of Office-based Opioid Treatment on Emergency Visits and Hospitalization in Adolescents with Opioid Use Disorder.

OBJECTIVE: To determine if engagement in office-based opioid treatment decreases emergency department, urgent care visits, and hospitalizations for acute opioid-related events (OREs) among adolescents with opioid use disorder. STUDY DESIGN: This retrospective cohort study identified all emergent and outpatient visits among adolescents, age 10-19 years, referred for office-based opioid treatment between January 1, 2006 and December 31, 2016. Patients were dichotomized into 2 cohorts: those who did and did not engage in office-based opioid treatment. The primary end point was the difference in the proportion of visits over the study period for acute OREs between cohorts and within the office-based opioid treatment cohort before and after referral. Secondary end points assessed change in the proportion of outpatient visits for treatment unrelated to opioid use disorder. RESULTS: Four hundred five emergent and outpatient visits were identified: 285 (70.4%) in the office-based opioid treatment cohort and 120 (29.6%) in the non-office-based opioid treatment cohort. After office-based opioid treatment engagement, 27.8% of visits in the office-based opioid treatment cohort were for acute OREs vs 80.8% in the non-office-based opioid treatment cohort (OR, 0.092; 95% CI, 0.052-0.160; P < .001). Outpatient visits in the office-based opioid treatment cohort were 10.9 times that of non-office-based opioid treatment (OR, 10.9; 95% CI, 6.23-19.16; P < .001). Within the office-based opioid treatment cohort, emergent visits decreased from 76.1% to 27.8% (OR, 0.121; 95% CI, 0.070-0.210; P < .001) and the odds of outpatient services was 8.3 times more after engagement (OR, 8.27; 95% CI, 4.78-14.4, P < .001). CONCLUSIONS: The absolute decrease in emergent visits for acute OREs was 53% in adolescents engaged in office-based opioid treatment, representing a relative decrease of 65.6% compared with adolescents not engaged. An analysis of visits before and after office-based opioid treatment demonstrated similar decreases, suggesting that office-based opioid treatment has a significant impact in decreasing acute OREs in the adolescent population.

Impact of Automated Targeted Medication Review Electronic Alerts to Reduce Potentially Inappropriate Medication Prescribing Among Medicare Enrolled Patients With Dementia.

BACKGROUND: Background:Finding ways to reduce prescribing of potentially inappropriate medications (PIMs) among patients with dementia is necessary. OBJECTIVES: To evaluate an automated targeted medication review (TMR) service to reduce PIM prescribing among patients with dementia. METHODS: This was a retrospective observational analysis of patients in a Medication Therapy Management (MTM) program for year 2017. Patients included if Medicare enrolled, MTM eligible, had dementia, and with PIM prescribing. Descriptive statistics described reduced PIM prescribing. Odds ratios (ORs) assessed prescriber relationship with PIM prescribing. Regression evaluated relationship between patient characteristics and discontinued PIMs. RESULTS: A total of 33 696 TMRs were triggered for 17 933 patients. Four months later, 11 608 TMRs led to a discontinued PIM among 8002 patients. Medications with the largest discontinuations were antihistamines (56%), muscle relaxants (53%), antiemetics (53%), and typical antipsychotics (40%). Physician primary care providers (PCPs) were more likely than nonphysician PCPs (OR = 4.54; 95% CI = 4.15-4.97; P < 0.001), psychiatrists (OR = 1.64; 95%CI = 1.44-1.86; P < 0.001), and neurologists (OR = 4.48; 95% CI = 4.07-4.93; P < 0.001) to prescribe medications to treat dementia and PIMs. Regression showed that younger age, female gender, higher poverty level, and a greater number of pharmacies, medications, and prescribers were associated with discontinued PIMs. Conclusions and Relevance: TMRs were effective in reducing PIM prescribing. Younger patients, individuals living in higher poverty levels, and patients with multiple prescribers or pharmacies may benefit most from this service. TMRs in primary care offices may reduce PIM prescribing.

Relationship between patient characteristics and number of phone calls to complete a telehealth comprehensive medication review: A cross-sectional analysis.

OBJECTIVE: To assess the relationship between patient characteristics and completion of telehealth comprehensive medication reviews (CMRs). DESIGN: Cross-sectional analysis of a national telehealth medication therapy management program. A negative binomial regression assessed the relationship between number of phone calls to complete a CMR and age, sex, number of medications, poverty level, geographic region, limited English proficiency (LEP), years eligible for CMR services, and if a caregiver completed the CMR. SETTING AND PARTICIPANTS: Patients included in the analysis were Medicare enrolled, medication therapy management eligible, and completed a CMR in 2017. Patients excluded if they were younger than 65 years, they had incomplete data, they had participated in an employer-sponsored plan, or completed a CMR with their provider. OUTCOME MEASURES: Number of phone calls reflected number of outgoing phone calls needed to complete a CMR. RESULTS: Analysis included 222,163 patients. Females needed 9% more calls to complete a CMR than males (incident rate ratio 1.09 [95% CI 1.08-1.10]). Adults older than 75 years compared with patients between age 65 and 74 years needed 7% fewer calls (0.93 [0.92-0.94]). Patients needing a caregiver to complete the CMR required 33% more calls than individuals who did not (1.33 [1.31-1.35]). Patients eligible for CMR services longer than 1 year required 12%-45% fewer calls to complete a CMR than recently eligible patients. A statistically significant interaction was detected between LEP and poverty quintile. CONCLUSIONS: This study found that poverty level inversely affected the number of phone calls to complete a CMR between those considered LEP and English language-speakers. Female sex and caregiver presence were associated with number of phone calls needed to complete a CMR. Older age and length of CMR eligibility were inversely associated with the number of phone calls needed. Future research is warranted to evaluate whether targeted approaches may improve CMR completion rates.

Antimicrobial Pharmacotherapy Management of Urinary Tract Infections in Pediatric Patients.

Objective: To discuss the risk factors, microbial resistance rates, and pharmacotherapy, including antimicrobial choices and medication dosage regimens, for urinary tract infections (UTIs) in pediatric patients. Data Sources: A MEDLINE literature search (1985 to December 2017) was performed using the following keywords and associated medical subject headings: urinary tract infection, antimicrobial, treatment, and children. Study Selection and Data Extraction: Search was conducted to identify clinical trials, systematic reviews, and guidelines. Search was filtered to include studies with age range between birth and 18 years and published in English. Additional references were identified from selected review articles. Data Synthesis: In total, 27 studies investigating microbial resistance, 31 studies assessing antimicrobial efficacy, 34 studies describing prophylaxis, and 6 systematic reviews were included. The resistance patterns differed across age groups and affected the choice of empirical therapy. If pyelonephritis is suspected, empiric antimicrobials should have high urinary and sufficient parenchymal concentrations. Nitrofurantoin has low microbial resistance rates and can generally be used empirically for treating uncomplicated cystitis in children >1 month of age. Trimethoprim-sulfamethoxazole resistance has increased and should be avoided unless local susceptibility data are available. Certain patients with recurrent UTIs or renal abnormalities may require antimicrobial prophylaxis, which may be associated with adverse effects, such as intolerability or an increased risk of microbial resistance. Conclusion: The resistance pattern of uropathogens should be considered prior to initiating therapy. Controlled trials with large samples are needed to compare the treatment duration of various antimicrobial regimens and the specific role of prophylactic antimicrobials.

Rising Cost of Anticancer Medications in the United States.

With more than 1.6 million new cases of cancer occurring each year, anticancer medications are in high demand. Escalating prescription drug prices have become a significant concern. Anticancer medications are among the most expensive prescription medications, many of them exceeding $100 000 a year. The survival benefits of certain newer anticancer medications may be a few months more than that from the existing treatment but at a much higher price tag. Drug cost may play a substantial role in making treatment choices. Multiple factors leading to high prices and some potential solutions to lower them have been highlighted.

Asthma as a Comorbidity in Hospitalized Patients: A Potential Missed Opportunity to Intervene.

Asthma is a frequent comorbidity in hospitalized children and adults. Patients with a history of asthma may have no breathing complaints or abnormal chest exam findings to trigger care for this comorbidity during hospitalization. Consequently, this may lead to a potential missed opportunity to discuss asthma as a comorbidity and ongoing issue to ensure its optimal management at home. Our goal is to raise awareness that such patient encounters may represent opportunities for health care professionals to optimize asthma management. Despite focusing on the present illness and limited time availability, asthma care may be improved in a time-efficient manner in these patients.

Complexities of Clinical Decision Support Illustrated by Pediatric Dosing Alerts.

Health information technologies, such as computerized clinical decision support (CDS) systems, are being utilized increasingly in pediatric health care institutions as a means of medication error prevention. Most studies have suggested a positive impact of CDS on medication safety, but others have identified complexities that have prevented full optimization of these systems. Recent studies regarding the implementation of pediatric dosing alerts have illustrated the complexities that can be associated with the design, implementation, and refinement of CDS systems. Although CDS dosing alerts have likely improved the safety of medication use in pediatric patients, it is important to be aware of certain limitations of the dosing alert systems. A collaborative effort is required to optimize the effectiveness of CDS dosing alerts.

Medication management of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex syndrome that is difficult to manage. Here we present the evidence supporting medication treatments for specific IBS symptoms, discuss evidence-based management of IBS with medications including dose regimens and adverse effects and review progress on research for new IBS treatments. SUMMARY: Currently, there is evidence to support improvements in specific IBS symptoms following treatment with loperamide, psyllium, bran, lubiprostone, linaclotide, amitriptyline, trimipramine, desipramine, citalopram, fluoxetine, paroxetine, dicyclomine, peppermint oil, rifaximin, ketotifen, pregabalin, gabapentin and octreotide and there are many new medications being investigated for the treatment of IBS. Key Message: Of the medications with demonstrated improvements for IBS symptoms, rifaximin, lubiprostone, linaclotide, fiber supplementation and peppermint oil have the most reliable evidence supporting their use for the treatment of IBS. Onset of efficacy for the various medications has been noted to be as early as 6 days after initiation; however, the efficacy of most medications was not assessed prospectively at predefined periods. Additional studies of currently available and new medications are ongoing and are needed to better define their place in therapy and expand therapeutic options for the treatment of IBS. The most promising new medications for IBS include a variety of novel pharmacologic approaches, most notably the dual µ-opioid receptor agonist and δ-opioid antagonist, JNJ-27018966.

Quantity, Duration, Adherence, and Reasons for Dietary Supplement Use among Adults: Results from NHANES 2011-2018.

Dietary supplement use is common among US adults. We aimed to investigate the quantity, duration, adherence, and reasons for supplement use in individuals who take supplements. Data from 2011 to 2018 from the National Health and Nutrition Examination Survey (NHANES) dataset were analyzed. Four cycles of data were combined to estimate these outcomes. Results are presented as overall group and by subgroups. All analyses were weighted to be nationally representative. The Taylor Series Linearization approach was used to generate variance estimates. A total of 12,529 participants were included. Over 70% of these individuals reported taking more than one unit of dietary supplements daily. Notably, approximately 40% had been taking supplements for more than five years and about 67% were highly adherent to at least one supplement. However, only 26.9% of these supplements were taken following a doctor's recommendation. The primary reasons for dietary supplements intake included improving overall health (37.2%), maintaining health (34.7%), bone health (21.4%), and diet supplementation (20.3%). Our findings indicate that most participants proactively used multiple dietary supplements focused on self-managed health and prevention, with substantial dedication to long-term use and high adherence. Healthcare professionals should play a more active role in guiding such behaviors to optimize the health outcomes of dietary supplement users across the United States.

Efficacy and safety of tirzepatide versus placebo in overweight or obese adults without diabetes: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tirzepatide was approved to treat type 2 diabetes and obesity, but its efficacy and safety in patients without diabetes has not been investigated. AIM: This meta-analysis aimed to evaluate the efficacy and safety of tirzepatide compared to placebo in overweight or obese patients without diabetes. METHOD: PubMed, Embase and Cochrane were searched on January 18, 2024. Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included. Efficacy outcomes included the proportion of participants achieving weight loss targets, changes in body weight (%), body mass index (BMI), waist circumference (WC), and blood pressure (BP). Safety outcomes were commonly reported adverse events. Standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CIs) were used for continuous and dichotomous outcomes, respectively. RESULTS: Three RCTs with 3901 participants were included. Tirzepatide was associated with increased proportion of participants achieving weight loss targets, reduced body weight (SMD - 1.61, 95% CI - 2.20 to - 1.02), BMI (SMD - 2.13, 95% CI - 3.08 to - 1.18), WC (SMD - 0.91, 95% CI - 1.14 to - 0.69), and BP versus placebo. However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo. CONCLUSION: Tirzepatide significantly reduced weight and improved metabolic markers among overweight or obese without diabetes. However, increased adverse events highlights the need for benefits versus risks assessment before initiation and continuous monitoring.

Comparative Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity or Overweight: A Systematic Review and Network Meta-Analysis.

Four glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used in children and adolescents with obesity or overweight. This network meta-analysis was conducted to compare the efficacy and safety of these regimens. Embase, PubMed, and Scopus were searched on March 2023 and updated in June 2024 for eligible randomized controlled trials (RCTs). The primary efficacy outcomes were mean difference in actual body weight, BMI (body mass index), BMI z score, and waist circumference. Safety outcomes included nausea, vomiting, diarrhea, abdominal pain, injection-site reaction, and hypoglycemia. Eleven RCTs with 953 participants were eligible. Semaglutide exhibited greater effects in reducing weight, BMI, and BMI z score versus the placebo. Semaglutide was associated with greater weight loss and BMI z score reduction in comparison with exenatide, liraglutide, and dulaglutide. Semaglutide also significantly decreased BMI than exenatide. None of the four GLP-1 RAs were associated with higher risks of diarrhea, headache, and abdominal pain versus the placebo. Liraglutide was more likely to cause nausea, vomiting, hypoglycemia, and injection-site reactions than the placebo. Liraglutide also had higher odds of causing injection-site reactions than other GLP-1 RAs. Semaglutide appeared to be the most effective and safe option among four GLP-1 RAs in children and adolescents with obesity or overweight.