The rising global burden of type 2 diabetes mellitus, compounded by the expanding therapeutic landscape, has placed increasing pressure on health systems to generate robust evidence on the long-term value for money of newer antidiabetic drugs (NADs). This systematic review addresses the urgent need for an updated synthesis of evidence on long-term health economic evaluations of NADs for the treatment of type 2 diabetes, including studies on the latest agents such as tirzepatide and finerenone. It aims to synthesise global long-term cost-effectiveness analyses, assess reporting completeness using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 framework and outline key implications for clinicians, payers and policymakers seeking to optimise type 2 diabetes management within resource-constrained health systems. PubMed, Embase, Cochrane, EBSCOhost, Scopus and Web of Science were systematically searched for studies published between 1 January, 2008 and 20 February, 2025. Eligible studies were long-term incremental cost-effectiveness analyses conducted in adults with type 2 diabetes, comparing NADs with other NAD classes or with standard treatment, and reporting outcomes such as incremental cost-effectiveness ratios. A formal risk of bias assessment using tools designed for clinical trials was not undertaken. Instead, reporting quality and transparency were assessed using the CHEERS 2022 checklist, with modelling-related sources of uncertainty and potential bias examined qualitatively. Given the methodological heterogeneity, results were synthesised narratively. Full-text English articles were included. This review was not prospectively registered. The search identified 1481 records, of which 142 studies met the inclusion criteria. Overall, 81% of incremental cost-effectiveness ratio-based analyses reported that NADs were cost effective compared with conventional therapies under country-specific willingness-to-pay thresholds. Using Thailand as an example of a developing country, studies generally found NADs not to be cost effective, largely because willingness-to-pay thresholds (USD 4336-5310 per quality-adjusted life-year) are substantially lower than those in higher income settings. Recently introduced agents (e.g. tirzepatide and finerenone) and early-line use were typically cost effective only at higher willingness-to-pay thresholds (USD 100,000-150,000 per quality-adjusted life-year) or following substantial price reductions (≥70% for sodium glucose cotransporter-2 inhibitors and ≥90% for oral glucagon-like peptide-1 receptor agonists). Most evaluations employed established diabetes models and adopted lifetime horizons from a payer perspective, while reporting quality assessments revealed limited disclosure of stakeholder involvement. These findings should be interpreted cautiously given the substantial heterogeneity across studies and methodological limitations inherent to long-term economic modelling. Overall, NADs generally provide favourable long-term cost effectiveness, owing to their cardiovascular and renal benefits; however, recently introduced agents and early-line use tend to be cost effective only at higher willingness-to-pay thresholds or after significant price reductions. Future evaluations should integrate real-world evidence and advanced modelling to capture long-term impacts and incorporate context-specific affordability considerations to support equitable and sustainable adoption of newer antidiabetic therapies.

Liver cirrhosis profoundly alters pharmacokinetics and is frequently associated with medication-related problems. Stage-specific dosing guidance remains inconsistent, and prescribing information often lacks clarity. As a result, treatment decisions rely on individual clinical judgement and may differ between professional groups. This study assessed drug-selection and dose-adjustment practices among hepatologists, clinical pharmacologists, and clinical pharmacists, quantified consensus across Child-Pugh stages, and evaluated alignment with prescribing information as a basis for harmonised dosing guidance. Twelve experts from hepatology, clinical pharmacology, and clinical pharmacy evaluated prioritised drugs for patients with liver cirrhosis across Child-Pugh stages A-C in a structured survey. For each drug, experts indicated whether they would apply no dose adjustment, modify the dose, or avoid administration. Consensus was defined as at least 75% agreement, and interrater agreement was assessed by pairwise percentage agreement. Consensus recommendations were compared with the dosing information provided in each drug's Summary of Product Characteristics. Consensus or strong consensus was achieved for only 20% of 177 recommendations, mainly for no dose adjustment or avoidance. Agreement decreased with disease severity (Child-Pugh A 83%; B 47%; C 41%). Of 36 consensus recommendations, 18 matched the summary of product characteristics, while six diverged from it. Pharmacists and clinical pharmacologists more often recommended dose adjustments, especially in Child-Pugh B and C, whereas hepatologists preferred standard dosing or avoidance. Expert recommendations for dosing in cirrhosis showed marked variability and limited concordance with prescribing information, underscoring the need for harmonised interdisciplinary guidance integrating pharmacokinetic evidence and clinical feasibility.

Linperlisib, a highly selective PI3K-δ inhibitor, was firstly approved in China in November 2022 for the treatment of patients with relapsed or refractory follicular lymphoma (r/r FL) who had received at least two prior lines of systemic therapy (3L+ FL), demonstrating compelling clinical efficacy. This study aimed to evaluate the cost effectiveness of linperlisib compared to duvelisib for patients with 3L+ FL from the perspective of Chinese healthcare system. A lifetime three-state partitioned survival model was developed to integrate comparative efficacy and direct costs. An unanchored matching-adjusted indirect comparison (MAIC) was conducted using individual data from NCT04370405 and published aggregate data from the DYNAMO trial, aiming to derive comparative efficacy data and calculate patients' life-years gained. Utility values were from GADOLIN study, as neither trial collected them. Quality-adjusted life-years (QALYs) were calculated by multiplying life-years by utility values. Direct costs included costs of drug acquisition, adverse events, subsequent salvage therapy, health-care resource use (HCRU), and end-of-life care. A 5% annual discount rate was applied to both future QALYs and costs. The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated as discounted incremental costs divided by incremental QALYs. The willingness-to-pay (WTP) threshold was set at China's 2023 per capita GDP (CNY89,358/QALY), with an ICER below this threshold indicating linperlisib was more cost effective. Model robustness was verified via one-way deterministic and probabilistic sensitivity analyses (DSA and PSA). In the base-case analysis, linperlisib yielded an additional 1.58 QALYs (4.13 vs 2.55) at an incremental cost of CNY108,780 (CNY292,805 vs CNY184,025) compared with duvelisib. The resulting ICER was CNY68,996 per QALY, which was below the WTP. Although drug costs were the main cost driver, improved survival reduced end-of-life care costs by CNY1,507. Deterministic sensitivity analysis identified the price of linperlisib as the top influential parameter, yet all ICERs stayed below the WTP threshold. Probabilistic sensitivity analysis showed a 91.2% cost-effectiveness probability at the preset WTP, confirming robust findings. Linperlisib is cost effective compared to duvelisib for 3L+ FL patients in China, as verified in sensitivity analyses. Further study is warranted to confirm that it meets an unmet need in China.

Vitiligo is challenging to treat and may have a substantial impact on quality of life. Despite the exponential growth in the development of new "traditional" vitiligo treatments, many vitiligo patients choose to employ medical products and practices that are used with or instead of standard medical care (complementary and alternative medicine or CAM). In this study, CAMs and camouflage were discussed together and referred to as over-the-counter products (OTCs). Using an observational cross-sectional study, we aimed to investigate the motivations and demographic factors of individuals with vitiligo who use OTCs, to identify the most utilized OTCs in this population, and to assess side effects and perceived efficacy of the utilized OTCs. We performed an international observational cross-sectional study between July 2021 and June 2022. An anonymous digital questionnaire was distributed to adults (aged ≥ 18 years) who had been diagnosed with vitiligo by a healthcare provider via e-mails from the Global Vitiligo Foundation to vitiligo support groups and through postings on the MyVitiligoTeam social media network. Participants were presented with a predefined list of OTC products and an open-ended option was also provided. Of the 224 respondents, half were aged 45-64, most were female (69.6%), and the majority were White (56.3%). A total of 41.1% of participants used OTCs, either exclusively (19.2%) or with prescribed therapies (22%), while 58.9% used only prescribed therapies. The top reasons for using OTCs were dissatisfaction with conventional therapy, concerns about side effects, inconvenience, and cost. The most commonly used OTCs were camouflage, Vitamin B12, Vitamin D, zinc, ginkgo biloba, and vitamin C. Camouflage was reported as the most helpful OTC. Mild side effects were reported by 6.3% of users. This study highlights the widespread use of OTCs in managing vitiligo, emphasizing the need for healthcare providers to be familiar with commonly used OTCs. Patients using OTCs raised concerns about conventional treatments, which should be considered in management discussions and drug development. Camouflage was the most beneficial OTC in this study, and it should be included in management plans. A better understanding of OTCs could improve treatment strategies and patient satisfaction.

Patients experiencing severe exacerbation (SE) of chronic obstructive pulmonary disease (COPD) face high re-hospitalization and mortality rates. Knowing their impact on health services is crucial for making decisions and improving the care pathway for these patients. To describe mortality, re-hospitalizations and therapeutic patterns of patients experiencing SE, this study used real-world Italian administrative data and examined pre- and post-SE treatment patterns. From an Italian administrative database (4.6 million inhabitants), patients with COPD in 2022 were identified, and those experiencing SE requiring hospitalization were described in terms of demographics, comorbidities, 12-month mortality and re-hospitalization rates, and therapeutic patterns during 12 months pre- and post-SE. Treatment patterns included dispensations of single-inhaler (SI, i.e., fixed-dose combination) triple therapy (TT), multiple-inhaler (MI, i.e., open combination) TT, dual therapy (DT; based on combinations between inhaled corticosteroid/long-acting beta-agonist/muscarinic antagonist), other respiratory treatment strategies, and no treatment. Among 81,571 patients with COPD (32.1 per 1000 inhabitants aged ≥ 45 years), patients experiencing SE were 6.2% (5080 patients with COPD): mean age was 77 years, 63.4% (3220 patients with SE) were male and 68.2% (3467 patients with SE) had ≥ 3 comorbidities. Mean in-hospital length of stay was 11.9 days. One-year mortality rate was 25.6% (1302 patients with SE), mainly within the first month, 76.0% (989 deaths) of which occurred in hospital. Among 12-month analysable patients (3778), the 12-month re-hospitalization rate was 20.1% (761 patients with SE and alive) occurring, on average, at 155 days (16.4% within the first month). Pre/post SE, single-inhaler triple therapy (SI-TT) and multiple-inhaler triple therapy (MI-TT) increased from 1.4 to 23.4% and from 1.2 to 6.3% patients, respectively; DT, other strategies, and no treatment reduced from 24.5 to 22.5%, 35.7 to 23.8% and 37.1 to 24.0%, respectively. On average, TT was initiated at ≥ 31 days post-SE. Mean time to TT initiation was approximately 31-42 days depending on prior therapy, although most patients initiated TT within the first 30 days. A substantial proportion of patients experiencing SE of COPD were re-hospitalised or remained inadequately treated or untreated, despite a high mortality rate. These findings underscore the necessity for a more appropriate and prompt therapeutic intervention.

In clinical trials, osimertinib combined with chemotherapy has demonstrated improved efficacy in patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. However, the projected long-term outcomes and the associated cost effectiveness compared to osimertinib monotherapy and first-generation EGFR-tyrosine kinase inhibitors remain uncertain. A lifetime partitioned survival model was developed from the US healthcare sector perspective using clinical trial data from pivotal trials FLAURA and FLAURA2. Model inputs included drug costs, administration costs, and health utilities sourced from the published literature. Dynamic drug pricing and a 3% discount rate were incorporated. Outcomes included life-years, quality-adjusted life-years (QALYs), total costs, and incremental cost-effectiveness ratios. One-way and probabilistic sensitivity analyses were performed. Combination therapy yielded 2.96 QALYs at a cost of $692,796. The resultant incremental cost-effectiveness ratio was $265,601/QALY versus osimertinib monotherapy and $467,747/QALY versus first-generation EGFR-tyrosine kinase inhibitors. Findings were consistent across sensitivity analyses. While clinically effective, based on commonly accepted cost-effectiveness thresholds in the USA, our study suggests that osimertinib plus chemotherapy was not cost effective compared to osimertinib alone or first-generation EGFR-tyrosine kinase inhibitors.

Pulmonary arterial hypertension is a rare, progressive pulmonary vascular disease with limited therapeutic options. MN-08, a nitrate derivative of memantine, is under development for pulmonary arterial hypertension. The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of MN-08 in healthy Chinese volunteers following single- and multiple-dose administration. A phase I, single-center, randomized, double-blind, placebo-controlled study was conducted using dose-escalation designs for both single ascending doses (6-132 mg, n = 69) and multiple ascending doses (12-36 mg twice daily for 7 days, n = 30), and a crossover design for the food effect evaluation (24 mg, n = 18), with an 8-day wash-out interval between periods. Healthy Chinese volunteers aged 18-45 years were enrolled. Safety was monitored continuously from screening through to the end of the study, with adverse events recorded throughout. The study endpoints were the pharmacokinetic parameters of MN-08 following single-dose, multiple-dose, and high-fat/high-calorie breakfast administration. All pharmacokinetic parameters were performed using a non-compartmental analysis with Phoenix WinNonlin® Version 8.2 (Certara USA, Inc., Princeton, NJ, USA). After a single dose of MN-08, the median time to maximum plasma concentration was 3.0-6.1 h and the mean half-life was 20.8-30.9 h. The mean maximum plasma concentration was 3.5-95.0 ng/mL. The mean area under the concentration-time curve (AUC) from the time of dosing to the last quantifiable concentration was 84-3428 h·ng/mL and the AUC from zero to infinity was 114-3618 h·ng/mL across all doses. In the multiple ascending dose study, the median time to maximum plasma concentration was 4.6-5.8 h and the half-life was 26.9-31.7 h. The mean maximum plasma concentration was 31.6-132.9 ng/mL. The mean AUC from the time of dosing to the last quantifiable concentration was 1291-5770 h·ng/mL and the AUC from zero to infinity was 1371-6237 h·ng/mL. Consumption of a high-fat and high-calorie meal had a minor effect on the peak concentration of MN-08. Drug accumulation was observed in the multiple ascending dose study and the mean accumulation index ranged from 3.76 to 4.33. There was no significant trend indicative of a sex effect. MN-08 was well tolerated in these healthy subjects. All adverse events were mild or moderate and no drug-related serious adverse events were reported. MN-08 exhibited favorable pharmacokinetic characteristics and a good safety and tolerability profile in healthy Chinese subjects across the evaluated dose range. These findings support the progression of MN-08 to phase II studies for the treatment of pulmonary arterial hypertension in Chinese patients. ChiCTR.org.cn identifier number ChiCTR2000031414.

Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, which may extend to total scalp (AA totalis) or whole-body hair loss (AA universalis). Nail involvement, though often underestimated, occurs in up to 66% of cases, especially in severe forms and in children. This retrospective study evaluated the efficacy of baricitinib 4 mg/day, a Janus kinase 1/2 inhibitor, in treating nail manifestations associated with severe AA. Thirty-seven patients with very severe AA (Severity of Alopecia Tool [SALT] score > 50) and nail involvement were treated with baricitinib for 48 weeks. Nail changes assessed included trachyonichia, pitting, leukonychia, and others. Clinical assessments were performed at baseline and at 12, 24, 36, and 48weeks using the SALT score, onychoscopy, and the Clinician Reported Outcome (ClinRO) for nail appearance. A significant improvement in both hair regrowth and nail abnormalities has been shown. The mean SALT score decreased from 100 to 16.3, and the average number of affected nails reduced from 6.4 to 2.1 (p < 0.001). ClinRO scores also significantly improved (p < 0.001). However, the correlation between hair and nail improvement was weak and not statistically significant (r = 0.15, p = 0.6). This suggests differential responsiveness of hair and nail units. The findings support baricitinib as a promising treatment for nail involvement in AA, highlighting the need for routine nail assessment and development of more refined evaluation tools. Limitations include small sample size and lack of long-term data.

Diabetic macular edema (DME) is a leading cause of vision impairment in individuals with diabetes, often treated with anti-vascular endothelial growth factor (anti-VEGF) therapies, such as Avastin® (bevacizumab) and Eylea® (aflibercept). The study objective is to assess the cost-effectiveness of bevacizumab and aflibercept under treat-and-extend (T&E) and pro re nata (PRN) regimens in managing DME in a real-world clinical setting. A field-based retrospective study was conducted at a public tertiary eye hospital in Baghdad, Iraq, from October 2024 through March 2025. The study employed a retrospective design, extracting clinical and treatment data from patients' medical records. Additional economic and sociodemographic information was collected through face-to-face interviews conducted by the first author between October 2024 and March 2025. A total of 394 adult patients with DME were included and categorized into six groups; two loading doses groups (LD)-LD Avastin (n = 206) and LD Eylea (n = 188)-and four maintenance doses (MD) groups-T&E Avastin (n = 139), T&E Eylea (n = 124), PRN Avastin (n = 67), and PRN Eylea (n = 64). Clinical outcomes included best-corrected visual acuity (BCVA; measured as logarithm of the minimum angle of resolution [log MAR]) and central macular thickness (CMT). Costs were calculated from the payer's perspective, incorporating medication, and patient costs. Incremental cost-effectiveness ratios (ICERs) were computed for each regimen. The study included 394 patients, each with one eye affected by DME, categorized into six groups. Based on the chosen LD, 206 patients received six monthly LD of Avastin, and 188 patients received five monthly LD of Eylea. Thereafter, on the basis of the maintenance treatment regimen chosen (MD), 67 patients were assigned to the PRN Avastin treatment group, 64 patients were assigned to the PRN Eylea treatment group, 139 patients were assigned to the T&E Avastin group, and 124 patients were assigned to the T&E Eylea group. During the loading phase, Eylea LD achieved a significantly greater mean utility gain than Avastin LD (0.0909 ± 0.0117 versus 0.0221 ± 0.0106; p = 0.0001). In the maintenance phase, both T&E regimens provided significantly higher utility gains than PRN strategies. PRN Avastin yielded the lowest utility gain (0.0066 ± 0.0072), while PRN Eylea showed modest improvement (0.0278 ± 0.0148; p = 0.0001). Despite superior utility outcomes, Eylea-based regimens exceeded the willingness-to-pay threshold, whereas T&E Avastin remained the most cost-effective option. The study suggests that Avastin under the T&E regimen is the most cost-effective treatment for DME, providing significant savings while maintaining effective management of the condition. These findings can guide therapeutic decision-making for DME in resource-limited settings and countries.

Contrast-induced acute kidney injury (CI-AKI) observed after coronary angiography (CAG) requires preventive strategies guided by clinical judgment. Evidence is still lacking regarding the prevention of CI-AKI in patients undergoing coronary angiography. This study aimed to compare the effect of a high dose of N-acetylcysteine (NAC) plus preprocedural hydration, a high dose of atorvastatin (HDS) plus preprocedural hydration, or preprocedural hydration alone on the prevention of CI-AKI in patients undergoing elective coronary angiography. A prospective multi-armed randomized comparative study was conducted on elective patients undergoing CAG. Patients were randomly assigned to either control group [n = 40], who received hydration with 0.9% saline started just before contrast media injection and continued for 12 h at a rate 1.0 mL/kg/min after angiography; NAC group [n = 40], who received oral NAC 1200 mg daily started 5 days before angiography and good hydration; or HDS group [n = 40], receiving one oral dose of atorvastatin 80 mg 24 h before angiography and good hydration. CI-AKI was defined as an increase in serum creatinine of > 25% of baseline or an absolute increase of 0.5 mg/dL above baseline after 48 h. Incidence of CI-AKI and incidence of complications were assessed for all groups. The study included 120 patients. The incidence of CI-AKI was [32.5%] in the control group, [20%] in the NAC group, and [12.5%] in the HDS group. The incidence of CI-AKI was significantly lower in the high-dose statin group compared with the control group (risk ratio = 1.658; 95% CI 1.050-2.433). In-hospital clinical outcomes showed no statistical significance among the three groups. Both NAC and high-dose statins may reduce CI-AKI incidence in patients undergoing CAG, with statins showing more promising results. These findings support prophylactic strategies for CI-AKI prevention in high-risk patients undergoing CAG. In-hospital outcomes were comparable. Clinical-Trials.gov (ID; NCT06139952, Date; December 2023).