Annals of Pharmacotherapy

Atrial fibrillation (AF) is associated with an increased risk of stroke and heart failure (HF). Historically, rate control has been the preferred treatment strategy due to fewer adverse drug events, but emerging evidence suggests early rhythm control may offer mortality benefits. Despite this, a critical gap exists in understanding short-term outcomes of rhythm control.

Assess the impact of early rhythm control strategy in patients with new-onset AF on mortality, hospitalizations, or emergency room (ER) visits compared to rate control strategy.

Retrospective observational study of patients at least 18 years of age diagnosed with new-onset AF cared for in a large United States healthcare system. Patients with identifiable triggers were excluded. The primary outcome was rates of all-cause mortality, hospitalization, or ER visit for AF, atrial flutter (AFL), or HF at 30 days.

Four hundred sixty-three patients were included, 278 in the rate control group and 185 in the rhythm control group. The median follow-up duration across groups was 654.5 days. At 30 days post-diagnosis, the rate control group experienced a higher rate of the primary outcome (19.8% vs. 11.9%, P = 0.027). Cox proportional hazards model demonstrated that rhythm control was associated with a reduced risk of experiencing the secondary outcome (HR 0.759, 95% CI [0.582, 0.984], P = 0.042).

In patients with new-onset AF, early rhythm control was associated with a lower incidence of all-cause mortality, hospitalization, or ER visits. These findings underscore the importance of rhythm control in optimizing early AF management and improving patient outcomes.

Cyclosporine is an immunosuppressant extensively used for the prevention and treatment of graft-vs-host disease (GvHD) in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). Converting the administration route of cyclosporine from intravenous to oral is common in the early period of allo-HSCT. Various factors may have an impact on the conversion ratio of cyclosporine.

To evaluate the effect of converting administration route from intravenous to oral on cyclosporine exposure in pediatric allo-HSCT recipients.

Children who underwent allo-HSCT and were administered with cyclosporine for the prevention of GvHD were included. The cyclosporine trough concentration (C0), the trough concentration-dose ratio (CDR), and the conversion ratio were evaluated. Meanwhile, factors related to the bioavailability of cyclosporine were also investigated.

A total of 67 children with 280 concentrations were involved. The conversion ratio used in the study was approximately 1:2, and a significant decrease in cyclosporine CDR (110.5 vs 41.4 mg/kg per μg/L, P < 0.001) was observed. The overall bioavailability of cyclosporine was approximately 35%. Age younger than 3 years old (β = −10.70, 95% CI = −18.45 to −2.96, P = 0.007) and moderately increased transaminases (β = −17.95, 95% CI = −25.42 to −10.48, P < 0.001) had a significant impact on cyclosporine bioavailability.

A conversion ratio of 1:3 was found to be more appropriate for pediatric allo-HSCT recipients when switching cyclosporine from intravenous to oral administration. Children younger than 3 years old or with moderately increased transaminases had significant lower cyclosporine bioavailability. These results can assist in an individualized approach for patients undergoing cyclosporine formulation switching.

Teicoplanin is widely used to treat Gram-positive infections in adult cancer patients, but early attainment of recommended trough concentrations and clinical determinants of those concentrations are not well characterized in patients receiving standardized, high-dose loading regimens.

This study aimed to characterize day 4 teicoplanin trough concentrations and to identify clinical predictors of under- and over-target levels in adult cancer patients receiving a standardized high-dose loading regimen.

This retrospective study included adult cancer patients who received a standardized high-dose teicoplanin loading regimen (600 mg intravenously twice daily on days 1-2 and once on day 3) and had a post-loading trough measurement on day 4. Patients were classified as under (< 20 mg/L), within (20-30 mg/L), or over target (> 30 mg/L). Clinical variables were compared across groups, and multivariable Firth-penalized logistic regression analysis was used to identify factors associated with under- and over-target trough concentrations vs within-target ones.

The study included 211 patients: 71 (33.6%) in the under-, 112 (53.1%) in the within-, and 28 (13.3%) in the over-target group. Higher body weight and febrile neutropenia were associated with higher odds of under-target trough concentrations, whereas higher serum albumin was associated with lower odds; febrile neutropenia was associated with lower odds of over-target concentrations.

The fixed high-dose loading regimen of teicoplanin evaluated in this study achieves a day 4 trough concentration of 20 to 30 mg/L in about half of adult cancer patients. Higher body weight, febrile neutropenia, and lower serum albumin may help identify patients who require intensified loading and early therapeutic drug monitoring.

Oral step-down therapy for the treatment of gram-negative blood stream infections (GNBSIs) has been shown to be noninferior to full courses of intravenous (IV) therapy. Studies comparing oral fluoroquinolones, sulfamethoxazole-trimethoprim (SMX-TMP), and beta-lactams have reported similar treatment outcomes, but beta-lactam groups have been small, and efficacy has been questioned given lower oral bioavailability.

This study aims to evaluate the safety and efficacy of oral cephalosporins compared with penicillins for step-down therapy for the treatment of GNBSI.

This was a retrospective study in adult patients admitted for Enterobacterales GNBSI that were transitioned from IV antibiotics to an oral beta-lactam. The primary outcome was treatment failure. Secondary outcomes included components of the primary outcome, microbiological failure, antibiotic-associated adverse drug events (ADEs), and Clostridioides difficile infection (CDI).

Overall, 280 patients with GNBSI with step-down to an oral penicillin (n = 140) or cephalosporin (n = 140) were included. More patients in the cephalosporin group had a urinary source of infection (87.9% vs 62.1%, P < 0.001) and urinary abnormalities (40% vs 28.6%, P = 0.044). Treatment failure with oral cephalosporins was noninferior to penicillins (7.1% vs 7.1%; 95% confidence interval [–6.4, 6.4], P = 0.002). No significant differences were found for microbiological failure, antibiotic-associated ADEs, or CDI.

Oral cephalosporins were noninferior to oral penicillins as step-down therapy for Enterobacterales GNBSI. This represents the first comparison of oral beta-lactams for the treatment of GNBSI.

Inflammation-driven mechanisms play a central role in adverse outcomes after non-ST-elevation myocardial infarction (NSTEMI), yet simple, widely available biomarkers for early risk stratification remain insufficiently defined. Hemogram-derived indices and iron-related inflammatory markers may provide complementary prognostic information.

To evaluate the prognostic significance of the mean platelet volume-to-monocyte ratio (MMR) and serum ferritin in predicting major adverse cardiovascular events (MACE) in patients with NSTEMI, and to assess the association of angiotensin-converting enzyme (ACE) inhibitor therapy with clinical outcomes.

This prospective cohort study included 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023. All patients received dual antiplatelet therapy and high-intensity statins. The baseline evaluation included a complete blood count, serum ferritin, and C-reactive protein. MMR was calculated as the ratio of mean platelet volume to absolute monocyte count. Patients were followed for 12 months for the occurrence of MACE, defined as cardiovascular death, non-fatal myocardial infarction, urgent revascularization, stroke, or hospitalization for heart failure.

During follow-up, 103 patients (60.6%) experienced MACE. Admission MMR (18.1 ± 11.7 vs 13.2 ± 5.5; P = 0.003) and ferritin levels (284 ± 396 vs 152 ± 109 µg/L; P = 0.001) were significantly higher in patients with events. In multivariable analysis, both MMR (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.11; P = 0.008) and ferritin (OR 1.28 per 100 µg/L, 95% CI 1.10-1.55; P = 0.003) independently predicted MACE, while ACE inhibitor therapy was associated with a lower risk (OR 0.24, 95% CI 0.08-0.70; P = 0.01). The combined model demonstrated good discriminative performance (AUC 0.72; 95% CI 0.64-0.80).

Elevated admission MMR and ferritin were independently associated with a higher 1-year risk of MACE in patients with NSTEMI. ACE inhibitor therapy was associated with improved outcomes, although causality cannot be inferred. These findings suggest that readily available inflammatory biomarkers may complement established clinical parameters for early risk stratification and support continued guideline-directed pharmacotherapy in NSTEMI.

Pharmacotherapy with stimulant or nonstimulant medications is recommended as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). Among patients prescribed stimulants, concomitant opioid use may increase the risk of drug dependence, exacerbate comorbid conditions, and compromise treatment adherence. However, limited evidence exists on the risk factors for initial opioid prescription in this population.

To identify factors associated with incident opioid prescriptions among patients with ADHD prescribed stimulant therapy.

We conducted a retrospective cohort study using the Merative® MarketScan® Commercial Claims and Encounters Database (2010-2020). We identified patients with ADHD who initiated stimulant therapy and followed them for 1 year to assess incident opioid prescription. Cox proportional hazards models were used to evaluate factors associated with opioid initiation.

Among 380 494 patients with ADHD initiating stimulants (mean age: 21.2 years; 56.5% male), 14.2% received an opioid prescription within 1 year. Factors significantly associated with incident opioid prescription included age ≥35 years (adjusted hazard ratio [aHR]: 10.84; 95% CI: 10.43-11.26), gender(aHR [female]:1.29; 95% CI: 1.27-1.31), geographic region (aHR [West]: 1.58; 95% CI: 1.52-1.64), multiple chronic conditions (aHR: 1.61; 95% CI: 1.54-1.67), anxiety (aHR: 1.19; 95% CI: 1.17-1.22), depression (aHR: 1.16; 95% CI: 1.14-1.19), severe mental illnesses (aHR: 1.18; 95% CI: 1.13-1.23), substance use disorders (SUDs) (aHR: 1.69; 95% CI: 1.63-1.75). Receipt of behavioral therapy before ADHD pharmacotherapy (aHR: 0.89; 95% CI: 0.87-0.92) was associated with a lower risk of receiving incident opioid prescriptions.

Several demographic factors (e.g., age, gender, geographic region) and clinical factors (e.g., history of mental health conditions and SUDs) are associated with opioid initiation among stimulant-treated patients with ADHD. These findings may inform clinical strategies to mitigate unnecessary opioid exposure and associated harms.

Etrasimod is an oral sphingosine-1-phosphate receptor modulator evaluated for induction and maintenance therapy in moderately to severely active ulcerative colitis (UC). This meta-analysis aimed to assess the efficacy and safety of etrasimod in adults with active UC.

To assess the efficacy and safety of etrasimod as induction and maintenance therapy in adults with moderately to severely active UC.

A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing etrasimod with placebo in adults (≥18 years) with moderately to severely active UC was conducted by searching PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov through November 2025. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models; heterogeneity was assessed with I² and χ² statistics. Analyses were performed with RevMan 5.4.

Four RCTs, including 1239 patients (etrasimod = 826; placebo = 413) were analyzed. At 12 weeks, etrasimod significantly improved clinical remission (RR = 2.92, 95% CI 1.71-4.98; I² = 57%), clinical response (RR = 1.71, 95% CI 1.46-2.02; I² = 19%), endoscopic improvement (RR = 1.72, 95% CI 1.30-2.27; I² = 36%), and mucosal healing (RR = 3.11, 95% CI 1.72-5.62; I² = 54%). Beyond 40 weeks, etrasimod increased clinical remission (RR = 4.28, 95% CI 2.72-6.73; I² = 0%), clinical response (RR = 2.20, 95% CI 1.74-2.78; I² = 0%), endoscopic improvement (RR = 3.51, 95% CI 2.36-5.23; I² = 0%), mucosal healing (RR = 6.93, 95% CI 3.61-13.33; I² = 0%), and steroid-free remission (RR = 4.28, 95% CI 2.72-6.73; I² = 0%). Any treatment-emergent adverse event was slightly higher with etrasimod (RR = 1.15, 95% CI 1.04-1.28; I² = 0%), while serious adverse events (RR = 0.79, 95% CI 0.39-1.61; I² = 38%) and discontinuations due to adverse events (RR = 2.17, 95% CI 0.54-8.67; I² = 50%) did not differ significantly.

Etrasimod is effective in inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC, with an acceptable safety profile.

Intravenous fluids are commonly used in postcardiac surgery to maintain or increase intravascular volume. While volume expansion after cardiac surgery is often necessary, the optimal fluid type to use is not established.

The objective of the study is to evaluate cost-savings and clinical outcomes of an albumin minimization protocol for postcardiac surgery fluid resuscitation at a surgical intensive care unit in a community teaching hospital.

This was a single-center retrospective cohort study of patients who received fluid resuscitation after open heart coronary artery bypass surgery or valvular surgery while on cardiopulmonary bypass at a community teaching hospital between February 2021 and May 2022. Cohorts were split up prior to the implementation of an albumin minimization protocol that was implemented in September 2021. The primary outcome was the amount of albumin or crystalloid fluids received after surgery, and the overall cost of intravenous fluids after surgery. Secondary outcomes included 30-day mortality, acute kidney injury, hours on oxygen support, hours on vasopressors, multiple vasopressors used, perioperative blood product transfusions, and 72-hour surgery take back.

Of 434 total patients evaluated, 400 patients met criteria for inclusion. Baseline characteristics were balanced between the 2 groups. Average surgical time was shorter in the postprotocol arm. Per patient use of albumin decreased by 27.1 g (22.8-31.4) while crystalloid fluid use increased by 1 L (0.9-1.2) after implementation of the albumin minimization protocol. Average cost savings were approximately $178 per surgery. No statistically significant difference was seen in any of the secondary safety and efficacy outcomes.

This study adds to the body of literature suggesting that the use of an albumin minimization protocol after open heart cardiac surgery was safe and effective. A significant reduction in cost and utilization of albumin was seen in the study without affecting patient outcomes.

The Impella® is a continuous axial flow pump that utilizes a purge solution to create a positive pressure barrier and prevent pump thrombosis. Bicarbonate-based purge solution (BBPS) is currently Food and Drug Administration-approved specifically for patients who are unable to tolerate heparin or have a contraindication to heparin, but solution choice between BBPS and heparin-based purge solution (HBPS) varies in clinical practice.

This study aims to compare the efficacy and safety of the BBPS versus HBPS when BBPS is used as the standard of care. The major endpoint was a composite outcome of pump thrombosis, stroke, and bleeding events.

This study was a retrospective analysis at 2 tertiary academic medical centers within the same health system (IRB Protocol #2023P002761). Adult patients were included if they required an Impella® device and received either the BBPS or HBPS for at least 72 hours between July 2022 and October 2023. The major endpoint was a composite outcome of pump thrombosis, stroke, and bleeding events. Pump thrombosis was defined as incidence of 2 or more purge pressures greater than 800 mmHg, the use of thrombolytic purge solution, or thrombus noted on imaging. Minor endpoints included intensive care unit (ICU) mortality, ICU length of stay, and vascular complications.

A total of 178 patients were evaluated of which 66 were included. The composite outcome occurred in 23 of 38 patients (60.5%) in the BBPS group and 17 of 28 patients (60.7%) in the HBPS group (P = 0.99). There was no difference in pump thrombosis, stroke, or bleeding events between cohorts. Vascular events were noted in 5 (17.9%) of HBPS and 13 (34.2%) of BBPS group (P = 0.14). Additional minor endpoints were not significantly different between the groups.

This study found no differences in pump thrombosis, stroke, and bleeding events in the BBPS versus HBPS group. Although these findings are supportive of utilizing BBPS as standard of care, larger, multi-center studies are needed to confirm differences in bleeding or thrombotic outcomes.

With the shortage of innovator semaglutide or tirzepatide products resolved, compounding pharmacies can only legally sell unique products. Unique products could have a different route of administration or dosing, or could include additional pharmaceutical ingredients.

To identify and characterize compounded semaglutide and tirzepatide products that differ from available FDA-approved products.

We searched compounding sites between February 3, 2025, and March 20, 2025, using key terms [“compounded semaglutide,” “compounded tirzepatide,” and “compounded GLP-1s”] on Google looking for products with a strength, route of administration, and/or formulation that differed from commercially available products.

We identified 33 unique semaglutide and/or tirzepatide products. Two-thirds contained semaglutide, and one-third contained tirzepatide. Forty-eight percent of products contained either semaglutide or tirzepatide with some combination of cyanocobalamin, glycine, niacinamide, docusate, or ondansetron. The 17 single active ingredient products were provided in sublingual (82%) or oral disintegrating tablet (ODT) (18%) formulations. Only 18% of included compounded products reported information about beyond use date and preferred storage conditions. Twenty-eight percent reported preferred storage conditions.

We found little justification for adding nutrients or docusate sodium to combination subcutaneous semaglutide or tirzepatide products. There is a rationale for adding ondansetron, but evidence for subcutaneous administration is lacking. There is a rationale for fashioning sublingual or ODT formulations, but whether these formulations offer advantages over innovator oral tablets has not been determined. The popularity of these products as an alternative to FDA-approved medications is concerning, given the lack of evidence for safety and efficacy.

Guidelines recommend arginine vasopressin (AVP) at a fixed dose for patients with septic shock who remain hypotensive after fluid resuscitation and norepinephrine, regardless of body weight.

This study seeks to evaluate whether body weight affects hemodynamic response (HDR) to AVP in critically ill patients with septic shock.

This was a single-center, retrospective cohort study of adult patients with septic shock. Patients received AVP at a fixed rate of 0.03 units/min in addition to catecholamine vasopressors and were grouped into 4 categories according to admission body weight. The primary endpoint was the time from AVP initiation to HDR, defined as a decrease in norepinephrine equivalents (NEEs) by at least 0.03 mcg/kg/min while maintaining a mean arterial pressure of at least 65 mm Hg for 1 hour. Secondary endpoints included a time to HDR defined as reduction in NEE of 0.05 mcg/kg/min, intensive care unit (ICU) length of stay (LOS), total duration of vasoactive agents, incidence of renal replacement therapy (RRT), and 28-day mortality.

A total of 170 patients were included in the study. No differences were observed between categories in time to HDR of 0.03 NEE (P = 0.854) or 0.05 NEE (P = 0.985). The total duration of vasopressors and ICU LOS were also similar between categories (P > 0.05). Patients weighing <75 kg had a lower incidence of RRT (P < 0.001) and patients weighing <100 kg had a lower 28-day mortality (P = 0.006). These findings remained significant after regression analysis.

Although body weight did not have a significant impact on the time to HDR, there was a significant difference in the incidence of RRT and 28-day mortality favoring those who weighed <75 and <100 kg, respectively. These findings contribute to the existing body of evidence, though larger trials are warranted to assess this further.

The use of the Calvert formula for carboplatin dosing is well established. However, controversy persists regarding the choice of kidney function estimation equations, with oncology and nephrology guidelines offering differing recommendations.

This study aimed to compare the actual carboplatin doses administered to patients with those estimated using various kidney function equations, and to assess whether these differences could influence clinical outcomes.

This retrospective chart review included adult patients who received at least 1 dose of carboplatin at our institution between May 2015 and March 2024. Carboplatin doses were estimated using the Calvert formula with different kidney function equations and compared with the actual doses administered.

A total of 360 patients met the inclusion criteria, with a median age of 57 years (46-68), a median weight of 72 kg (61-84), and 248 (68.9%) were female. Significant inter-method variability was observed in the median estimated kidney function and corresponding median carboplatin dosing across equations. Cockcroft-Gault (C-G) using actual body weight (110 mL/min, 677 mg), C-G with adjusted body weight (94 mL/min, 602 mg), 2021 CKD-EPI (chronic kidney disease epidemiology collaboration) (100 mL/min/1.73 m², 649 mg), 2021 CKD-EPI_BSAAdj (101 mL/min, 658 mg), and the Janowitz equation (83 mL/min, 577 mg), P < 0.001. Hematologic toxicity, including febrile neutropenia, was significantly more common in patients dosed using C-G equation with actual body weight compared with adjusted body weight, occurring in 14/20 (70%) versus 5/115 (4.3%), respectively (P < 0.001).

Carboplatin dosing varies significantly depending on the kidney function estimation method used. There is an urgent need for standardized, interdisciplinary dosing guidelines.

Pneumocystis jirovecii pneumonia (PJP) is increasingly recognized among immunocompromised adults without HIV, yet prophylaxis use remains inconsistent. Data describing cumulative and overlapping immunosuppressive exposures before PJP diagnosis are limited.

To characterize immunosuppressive exposure patterns and evaluate use of PJP-active therapy among non-HIV, nonhematopoietic cell transplant (non-HCT) adults with PJP.

This retrospective cohort study (2011-2024) used the TriNetX Research Network. Adults without HIV or prior HCT with laboratory-confirmed PJP (positive polymerase chain reaction or antigen from respiratory specimens) were included. Demographics, comorbidities, and exposure to glucocorticoids (GCs), antineoplastics (ANs), and immunosuppressants (ISs) within 90 days before diagnosis were assessed. Overlapping immunosuppressive regimens and their associations with receipt of PJP-active therapy were evaluated. Because prescribing indication and dosing were unavailable, prescriptions for trimethoprim/sulfamethoxazole, atovaquone, dapsone, or pentamidine were grouped as PJP-active therapy, representing prophylactic, preemptive, or empiric use.

Among 578 adults with PJP, 87% received GCs, 37% ANs, and 26% ISs. More than half (54%) were exposed to 2 or more drug classes, whereas 10% had no identifiable immunosuppressive medication exposure. Despite frequent multidrug immunosuppression, only 32% received PJP-active therapy before diagnosis. GC exposure was more common among patients who received PJP-active therapy (97% vs 82%, P < 0.001), while AN and IS exposures did not differ between groups.

PJP in non-HIV, non-HCT adults commonly occurs in the setting of frequent multidrug immunosuppression. These findings reveal a disconnect between cumulative immunosuppressive risk and prophylaxis practices and support approaches that incorporate overall immunologic burden rather than single-agent thresholds.

To review the efficacy and safety of gepotidacin for the treatment of uncomplicated urogenital gonorrhea (uUGG).

A literature search of PubMed and Google Scholar (January 2010 to January 2026) was conducted using the terms gepotidacin and GSK2140944. Additional sources included conference abstracts, the manufacturer’s website, and prescribing information.

Relevant English-language studies evaluating the efficacy and safety of gepotidacin for uUGG were included.

Gepotidacin is a first-in-class triazaacenaphthylene antibiotic with a novel mechanism of action and potent activity against Neisseria gonorrhoeae. In the phase 3 EAGLE-1 trial, gepotidacin demonstrated noninferiority to ceftriaxone plus azithromycin for uUGG treatment. It was generally well tolerated, with gastrointestinal adverse effects most commonly reported. Gepotidacin is administered as 3000 mg orally every 12 hours for 2 doses and is approved for adults and pediatric patients aged ≥12 years weighing ≥45 kg with limited or no alternative treatment options. Administration with food is recommended to reduce gastrointestinal adverse effects.

Gepotidacin provides a new 2-dose oral option for uUGG treatment. Compared with ceftriaxone, the current drug of choice, oral administration may improve convenience and access. Similar to cefixime and zoliflodacin, its oral formulation may facilitate treatment while potentially reducing microbiome disruption compared with ceftriaxone.

Gepotidacin is a promising oral antibiotic with a novel mechanism of action and demonstrated efficacy for uUGG treatment.

Urinary tract infections (UTIs) are the most common infection in kidney transplant recipients (KTRs), and the large increase in antibiotic-resistant pathogens is minimizing effective treatments. The objective of this study was to evaluate the safety and efficacy of fosfomycin for the treatment of culture-positive lower UTIs in KTRs.

A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards was conducted through June 2025 on Embase, PubMed, Cochrane Central Register of Controlled Trials, Web of Science Core Collection, and the Global Index Medicus.

The terminology used to create the search included UTIs and synonyms, fosfomycin and synonyms, and kidney transplant and synonyms. Patients with culture-positive lower UTIs, defined as either cystitis or asymptomatic bacteriuria and with documented clinical and microbiological cure data were included. Records with non-human, non-English, adolescents or children (<18), fosfomycin prophylaxis only, or upper UTI-only analyses were excluded.

Six studies were included for data analysis. A total of 564 culture-positive lower UTI episodes in KTRs were treated with fosfomycin monotherapy. Treatment regimens were generally multi-dose with various frequencies and durations. All studies reported results in the form of clinical cure, microbiological outcomes, and treatment-emergent adverse effects. Many of the causative pathogenic bacteria in the treatment intervention were multi-drug resistant (MDR) in nature.

The adequate treatment of UTIs in KTRs is imperative to long-term graft success, low mortality rates, and cost savings. Further randomized controlled trials (RCTs) are needed to assess fosfomycin use for MDR UTIs in this population. In aggregate, oral fosfomycin as monotherapy for UTIs in KTRs demonstrated positive outcomes regarding clinical cure, microbiological outcomes, and treatment-emergent adverse effects.

To evaluate the efficacy and safety of adding pioglitazone as a third-line agent in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and sodium-glucose cotransporter-2 inhibitors.

A systematic search of PubMed, Scopus, the Cochrane Library, and Google Scholar was conducted through February 2026 for randomized controlled trials (RCTs).

Eligible RCTs reported outcomes on glycemic control and cardiometabolic parameters. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk-of-Bias tool 2, with certainty of evidence evaluated using the Grading of Recommendations Assessment, Development, and Evaluation tool.

Four RCTs (n = 1213) were included. Using a random-effects model, pioglitazone significantly reduced glycated hemoglobin (HbA1c) (mean difference [MD]: −0.56%; 95% confidence interval −0.74 to −0.38; P < 0.00001) and increased the likelihood of achieving HbA1c <7% (risk ratio: 2.37; 95% CI 1.87-3.01). Subgroup analysis demonstrated a dose-dependent effect, with 30 mg providing greater glycemic reduction than 15 mg. Significant improvements were also observed in fasting plasma glucose, homeostasis model assessment of insulin resistance, triglycerides, high-density lipoprotein cholesterol, and diastolic blood pressure. However, pioglitazone was associated with weight gain (MD: 2.38 kg) and a higher risk of adverse drug reactions.

These findings suggest that pioglitazone is an effective add-on therapy for patients with T2DM who remain uncontrolled on metformin and SGLT2 inhibitors, particularly in those with significant insulin resistance. However, its use should be individualized, with careful consideration of predictable adverse effects such as weight gain and tolerability, rather than routine escalation for all patients.

Adding pioglitazone to metformin and SGLT2 inhibitors significantly improves glycemic control and metabolic parameters. While the 30 mg dose offers greater efficacy, clinicians must balance these benefits against predictable side effects like weight gain.

The objective of this systematic review and meta-analysis was to compare the efficacy and safety of glucagon-like peptide-1 (GLP-1) receptor agonists for the management of antipsychotic-induced weight gain.

A systematic review was conducted following PRISMA methodology through July 2025 that evaluated the efficacy and safety of GLP-1 agonists for the management of antipsychotic-induced weight gain.

Efficacy endpoints were change in body weight (kg), change in body mass index (BMI) (kg/m²), and change in HbA_1c (%). The safety endpoint was gastrointestinal (GI) adverse effects. A P-value of 0.05 was considered statistically significant, and heterogeneity was reported as I².

Six studies were included in this systematic review, of which 4 trials were included in the meta-analysis. The difference found between GLP-1 agonists and placebo was a change in weight of −5.85 kg (P = 0.0622, 95% CI = −9.72 to −1.97), a change in BMI of −2.11 kg/m² (P = 0.7692, 95% CI = −5.51 to 1.29), and a change in HbA_1c of −1.58 (P = 0.6659, 95% CI = −4.75 to 1.58). The overall risk ratio for a patient to experience a GI-related adverse effect when taking a GLP-1 agonist compared to placebo was 1.83 (95% CI = 1.42 to 2.37).

While the efficacy endpoints did not reach significance, this meta-analysis shows that select GLP-1 receptor agonists may be used to promote weight loss in patients taking antipsychotics. Controlling antipsychotic-induced weight gain helps patients remain adherent to therapeutic doses of their antipsychotic medications.

The use of certain GLP-1 agonists may be considered to help promote weight loss in patients experiencing antipsychotic-induced weight gain.