Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated protective effects against chronic kidney disease, their impact on acute kidney injury (AKI) remains unclear. AKI and chronic kidney disease share overlapping clinical features but differ in pathogenesis and risk profiles. Previous analyses often grouped diverse agents into single categories, potentially concealing medication-specific renal risks. Given the widespread assumption of renoprotection, particularly among newer agents, there is a need to evaluate the comparative AKI risk of GLP-1RAs and SGLT2is at the individual drug and dose level. We performed a Bayesian network meta-analysis (NMA) following Cochrane-recommended methodology for safety-focused assessments. A systematic literature search across eight databases identified 67 randomized controlled trials (RCTs), including 199,877 participants. Eligible trials reported AKI outcomes or sufficiently explicit acute renal injury-related events associated with GLP-1RA or SGLT2i interventions. The primary outcome was the incidence of AKI; all-cause dropout was analyzed as a general tolerability measure. Odds ratios (ORs) with 95% credible intervals (CrIs) were calculated, and surface under the cumulative ranking curves (SUCRA) were used to estimate relative safety rankings. Only high-dose tirzepatide (10-15 mg/week) was associated with a significantly increased risk of AKI compared to controls (absolute risk difference: 0.28%; number needed to harm: 357). In contrast, lixisenatide, high-dose canagliflozin (300 mg/day), empagliflozin, and dapagliflozin were associated with reduced AKI risk. Risk rankings consistently identified high-dose tirzepatide as the most likely to induce AKI. Subgroup analyses excluding patients with baseline renal impairment yielded consistent results. High-dose tirzepatide may elevate AKI risk despite its metabolic benefits. Clinicians should assess renal vulnerability when prescribing GLP-1RAs or SGLT2is, particularly in patients with preserved kidney function. Further prospective trials are needed to clarify causal mechanisms and inform clinical decision-making.

Climate change is increasingly affecting the ecological stability, cultivation conditions, and bioactive compounds of medicinal plants used in Traditional Chinese Medicine (TCM), raising concerns about resource sustainability and therapeutic reliability. This scoping review aims to map current evidence on climate-related impacts on TCM medicinal plants and to examine how such evidence may inform future sustainability-oriented regulatory approaches. Following framework developed by Arksey & O’Malley, major databases were searched from inception to December 2025 for studies examining environmental or climatic influences on TCM medicinal plant distribution, growth, yield, or phytochemical characteristics. Reported outcomes were synthesised into three fields consisting of herb availability, herb quality, and adaptation strategies. To support consistent botanical identification and explore regulatory implications, identified species were subsequently mapped to the Taiwan Herbal Pharmacopoeia (THP) as analytical framework. From 2457 screened studies, 74 met inclusion criteria. Global warming was shown to impact availability of botanical drugs with predictive models, with species like Gentiana manshurica projected to lose highly suitable habitats, while some (e.g., Leonurus japonicus) have expanded into new regions. Moderate drought stress was found to improve active compound synthesis, but prolonged stress decreased yield and quality in plants such as Panax notoginseng and Glycyrrhiza uralensis. However, existing studies that systematically address adaptation policies and protocols remain limited. Climate change poses a substantial challenge to the resilience and sustainability of TCM plants. Integrating climate vulnerability into pharmacopoeia standards and prioritizing interdisciplinary adaptation strategies are essential to safeguard the global supply and clinical efficacy of TCM botanical resources.

Research ethics and integrity are foundational to the credibility, safety, and societal trust of scientific inquiry. As the use of traditional, complementary, and integrative medicine (TCIM) grows globally, concerns about research misconduct (including fabrication, falsification, and plagiarism) have become increasingly salient. With up to 80% of populations in certain countries utilizing TCIM, the field’s expansion underscores the need for rigorous, ethically grounded evidence to guide practice and policy. However, around 470 TCIM-related articles have been retracted to date, as indicated on the Retraction Watch database, which may be due to ethical or non-ethical concerns. This educational article critically examines the state of ethics and integrity in TCIM research, drawing on case studies of misconduct and highlighting the broader consequences for patient safety, scientific credibility, and healthcare integration. In addition, the educational article explores emerging ethical dilemmas posed by artificial intelligence (AI), including risks of automated fabrication, falsification, plagiarism, and opacity in research reporting. To strengthen ethical conduct, we propose strategies spanning four domains: 1) improving education and fostering interdisciplinary collaboration to enhance research literacy, 2) embedding open science practices to promote transparency and reproducibility, 3) leveraging meta-research to monitor and advance research quality, and 4) developing policies and safeguards for responsible AI use. Upholding high ethical standards in TCIM research is essential not only to ensure reliable evidence but also to protect patients, sustain public trust, and enable meaningful integration of TCIM within evidence-based healthcare systems.

Acupoints have traditionally been regarded as specific loci along meridians for regulating Qi, Blood, and organ function. This review is a clinically oriented narrative review summarizing current evidence on the anatomical, neurophysiological, and clinical characteristics of acupoints. We first reviewed the structural basis of acupoints, including peripheral nerve endings, connective tissue planes, fascia, microvascular components, and immune-related elements. We then discussed how mechanical stimulation by acupuncture may be transformed into electrical, biochemical, and neural signals through mechanisms involving sensory afferents, endogenous opioids, neurotransmitters, adenosine, mast cells, and neuroimmune interactions. The concept of the Neural Acupuncture Unit was introduced as a framework for understanding acupoints as three-dimensional functional interfaces rather than simple surface points. We also examined the relationship between acupoints, Ashi points, myofascial trigger points, Five-Shu Points, Back-Shu Points, De-Qi sensation, needling depth, and acupoint sensitization. Finally, this review proposed that acupoints should be understood as dynamic cutaneous functional windows that reflect local tissue microenvironments and systemic physiological or pathological states. Further studies are needed to refine acupoint localization, safety assessment, and precision acupuncture practice.

Major Depressive Disorder (MDD) is characterized by heterogeneous pathogenesis that extends beyond traditional monoamine deficits. A paradigm shift is recognizing neuroinflammation as a central, critical driver of both illness onset and resistance to treatment. The CXCL12/CXCR4 system is traditionally associated with immune cell trafficking, but increasing evidence reveals its powerful regulatory role in neuropsychiatric disorders. We performed a comprehensive synthesis demonstrating that CXCL12/CXCR4 axis acts as a direct molecular modulator of neurotransmission, neuroplasticity, and glial cell signaling. Specifically, this axis can modulate a multiple molecular pathways linked with the glutaminergic, GABAergic, and serotonergic systems, and mediating neuroplasticity and glial cell function. Functionally, CXCL12/CXCR4 axis has twofold character - it can strengthen neurotoxic processes through overactivation of NMDAR and excessive Ca2 + influx. On the other hand, it can also play protective role by preventing excitotoxicity, supporting neurogenesis, enhancing GABA synthesis, and dendritic spines stabilization. This review focuses on identifying potential mechanisms across in vitro, animal, and human studies to establish the CXCL12/CXCR4 axis as a powerful biomarker and, critically, an unexploited therapeutic target.

Background:Artificial intelligence (AI) integration offers significant potential to improve mental healthcare, however, the reliability of large language models (LLMs) in performing nuanced clinical tasks remains an important and largely unanswered question. This study aimed to evaluate ChatGPT's performance in scoring the Hamilton Depression Rating Scale (HAMD-21) compared with expert raters using standardized patients (SPs). Methods:Three senior mental health experts created and portrayed scenarios for ten SPs representing diverse depressive symptom profiles. Recorded interviews were transcribed and used as input for ChatGPT-4o. HAMD-21 scores generated by ChatGPT were compared with those assigned by expert raters and with predefined script-based reference scores. Inter-rater reliability was assessed using intraclass correlation coefficient (ICC), and differences between raters were evaluated using Steiger's tests. Results:ChatGPT and the expert raters achieved good-to-excellent reliability for total HAMD-21 scores (experts: ICC = 0.9921; ChatGPT: ICC = 0.9739). However, expert raters achieved perfect ICCs on 11 individual items, whereas ChatGPT achieved perfect agreement on only 2 items. Steiger's test demonstrated that experts significantly outperformed ChatGPT on 10 individual items as well as on total scores (Z = 1.931, p = 0.0268). Qualitative review revealed that ChatGPT tended to overestimate scores on items related to insomnia and somatic symptoms (items 4-6 and 13) and frequently miscalculated total scores. Conclusions:ChatGPT demonstrated excellent agreement on total HAMD-21 scores in structured, text-based depression assessments, supporting the potential role of LLMs as adjunctive tools for standardized depression severity evaluation. However, item-level discrepancies and systematic scoring errors indicate that human oversight remains essential for clinically nuanced interpretation.

OBJECTIVE:Laughter therapy serves as a practical and efficient complementary alternative therapy for psychological distress. This meta-analysis aimed to further investigate the efficacy of laughter therapy by integrating trial sequential analysis (TSA) and exploring the optimal treatment duration using a dose-response meta-analysis. DATA SOURCES:This systematic review conducted randomized controlled trials across major databases (PubMed, EMBASE, PsycINFO, and the Cochrane Library), from their inception to November 12, 2023. Included articles using laughter therapy for depression, anxiety, stress, pain, or quality of life. We employed TSA to assess evidence conclusiveness and the dose-response meta-analysis to explore optimal treatment length. STUDY SELECTION AND DATA EXTRACTION:Thirty-three studies were included in the analysis. The following information was extracted: information on publication, patients' characteristics, intervention type, intervention duration. Information on outcomes (e.g., type of outcome, measurement tool) and statistical data needed for effect size estimation were extracted independently by two authors (THL & CYL). RESULTS:Laughter therapy significantly reduced depression (standardized mean differences [SMD] = -0.9; 95% CI: -1.29 to -0.52), anxiety (SMD = -0.83; 95% CI: -1.16 to -0.50), and stress (SMD = -0.68; 95% CI: -1.02 to -0.33) (all p < .001). The dose-response meta-analysis revealed that longer cumulative treatment durations up to 400 min for depression and 600 min for anxiety yielded greater improvements, with benefits plateauing thereafter. Our subgroup analyses showed that laughter-inducing therapies significantly alleviate depression, anxiety and stress across various ages, patient conditions, and care settings. CONCLUSIONS:Laughter therapy effectively alleviates depression, anxiety, and stress, with optimal durations identified for these benefits. The study strengthens the evidence base for laughter therapy and provide supportive evidence for conducting more future RCTs to clinical implication.

OBJECTIVE:Emerging evidence has shown that an exacerbation of oxidative stress and a reduction of antioxidant activity may be implicated in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Nevertheless, differences in methodologies (e.g., participant age, biological sample type, and analytical tools) across studies may be attributed to variations in the findings. Thus, meta-analysis is needed to systematically assess oxidative stress and antioxidant biomarkers in children and adolescents with ADHD. METHODS:Three electronic databases, including PubMed, Web of Science, and Embase, up to January 03rd, 2026, reporting data on the levels of oxidative stress and antioxidant biomarkers including total oxidant status (TOS), 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), nitric oxide (NO), total antioxidant status (TAS) and superoxide dismutase (SOD), measured in various biological sample types (e.g., urine, serum, and plasma) in children and adolescents with ADHD. Statistical analyses used standardized mean differences (SMDs) with 95% confidence intervals (CIs) under a random-effects model, with heterogeneity quantified by I2 and subgroup analyses by sample type. RESULTS:A total of 20 studies, comprising 1,325 children and adolescents with ADHD and 1,272 healthy controls. The pooled data across studies have demonstrated that ADHD patients have higher blood levels of TOS (SMD = 0.94; 95% CI = 0.63 to 1.25; p < 0.00001) and urinary levels of 8-OHdG (SMD = 0.21; 95% CI = 0.07 to 0.35; p = 0.004), when compared to healthy controls. However, there were no differences in blood levels of 8-OHdG (SMD = -0.26; 95% CI = -0.62 to 0.10; p = 0.15), MDA (SMD = 0.21; 95% CI = -0.87 to 1.29; p = 0.70), and NO (SMD = 0.03; 95% CI = -0.31 to 0.33; p = 0.84) between ADHD patients and controls. Regarding antioxidant activity, ADHD patients have lower blood TAS levels (SMD = -0.53; 95% CI = -0.99 to -0.08; p = 0.02). However, there were no differences in blood levels of SOD (SMD = -0.75; 95% CI = -1.97 to 0.46; p = 0.22) between ADHD patients and the healthy controls. CONCLUSION:The results indicate elevated blood TOS and urinary 8-OHdG levels and decreased blood TAS levels in children and adolescents with ADHD, further supporting a role for oxidative stress in the pathophysiology of ADHD.

BACKGROUND:Fibromyalgia is a frequently treatment-refractory chronic musculoskeletal pain disorder that often results in clinical depression; however, the role of neuroinflammatory signaling in comorbid depression remains unclear, including the contributions of anti-inflammatory omega-3 fatty acids like eicosapentaenoic acid (EPA). METHODS:This study examined the efficacy of EPA ingestion for reducing chronic pain and depression comorbidity (CPDC) in a mouse model established using intermittent cold stress. RESULTS:Our results showed that oral EPA could alleviate mechanical and thermal hyperalgesia in CPDC mice. The preventive effect of EPA on depressive symptoms in CPDC mice was further confirmed. Western blot and immunofluorescence staining revealed that EPA can inhibit the enhanced neuroinflammatory signaling concomitant with increased astrocyte and microglia activation and elevated levels of inflammatory signaling factors high-mobility group box 1 (HMGB1) and S100B in the CPDC mice. Alternatively, oral EPA can increase the attenuated expression of the pain-inhibiting programmed cell death protein 1 (PD-1) receptor. EPA intake can further alleviate inflammation-associated toll-like receptor 4 (TLR4) and downstream signaling molecules myeloid differentiation primary response 88 (MyD88), TNF receptor associated factor 6 (TRAF6), and activated (phosphorylated) nuclear factor kappa-light-chain-enhancer of activated B cells (pNFκB) in CPDC mouse brain. A similar response also observed in transient receptor potential vanilloid 1 gene knockout mice. CONCLUSION:This demonstration that oral EPA can prevent CPDC by inhibiting neuroinflammatory pathways could facilitate improved treatment strategies for CPDC.

BACKGROUND:Omega-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA), exhibit adjunctive antidepressant efficacy despite negligible detectable levels in the brain. Emerging evidence implicates specialized pro‑resolving mediators (SPMs); bioactive n-3 PUFA metabolites offer a coherent pathway by actively resolving inflammation, enhancing tissue repair, and supporting neuronal function. To test whether n‑3 PUFA supplementation activates pro‑resolving biology in humans, this meta‑analysis quantified effects on circulating SPM precursors. METHODS:We systematically searched PubMed, EMBASE, Web of Science, GOED, and the Cochrane Library (up to May 18, 2026) to identify RCTs examining the impact of n-3 PUFAs supplementation on circulating SPM precursors 18-hydroxyeicosapentaenoic acid (18-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHA). Meta-analysis was performed using Review Manager 5.4.1 with random-effects models. RESULTS:Eleven RCTs, comprising 810 participants, were included. N-3 PUFAs supplementation significantly and robustly increased the concentrations of both circulating SPM precursors: 18-HEPE (SMD = 1.05, 95% CI 0.54-1.55, Z = 4.08, P = 0.0001) and 17-HDHA (SMD = 0.69, 95% CI 0.19-1.18, Z = 2.72, P = 0.006). Importantly, subgroup analyses revealed that this increase was selectively amplified in patient populations characterized by a significant inflammatory, metabolic, and oxidative burden, including peripheral artery disease (PAD), chronic kidney disease (CKD), MDD with comorbid obesity, and pregnancy, but was negligible in healthy infants. CONCLUSION:N-3 PUFA supplementation significantly increased circulating 18-HEPE and 17-HDHA, indicating greater availability of upstream EPA- and DHA-derived SPM precursors across mixed human populations. However, whether these precursor changes translate into increased downstream SPM production or clinical antidepressant effects remains uncertain and requires dedicated trials in MDD populations. PROSPERO registration number: CRD420251138493.

BACKGROUND:Serotonergic antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are associated with an increased risk of hyponatremia, whereas mirtazapine appears to confer a lower risk. However, evidence regarding newer antidepressants, specifically agomelatine, remains limited. This study aimed to evaluate the risk of hyponatremia associated with agomelatine compared with mirtazapine, escitalopram, and venlafaxine. METHODS:This retrospective cohort study analyzed electronic medical records from Kaohsiung Veterans General Hospital. Antidepressant-naïve patients who initiated at least 2 weeks of monotherapy with agomelatine, escitalopram, venlafaxine, or mirtazapine between May 2013 and April 2023 were included. Hyponatremia was identified using serum sodium measurements. Multivariable logistic regression was performed to assess the association between antidepressant use and hyponatremia after adjusting for demographic, clinical, and medication-related factors. RESULTS:The incidence rates of hyponatremia were 5.8% for mirtazapine, 6.9% for agomelatine, 8.5% for escitalopram, and 10.2% for venlafaxine. In the univariate analysis, venlafaxine was associated with a higher risk of hyponatremia than was mirtazapine (odds ratio [OR] = 1.80, 95% CI: 1.09-2.97, p = 0.021). However, after adjustment, the risk of hyponatremia did not differ significantly among the antidepressants (agomelatine: adjusted odds ratio [aOR] = 0.79, escitalopram: aOR = 1.18, venlafaxine: aOR = 0.87; all p > 0.05). Independent predictors of hyponatremia included older age (aOR = 1.02, p < 0.001), malignancy (aOR = 2.52, p < 0.001), diabetes mellitus (aOR = 1.64, p < 0.001), and concomitant use of anticancer agents (aOR = 2.72, p < 0.001). CONCLUSION:These findings underscore the complexity of hyponatremia etiologies and highlight the need for individualized treatment strategies that account for comorbidities and potential drug interactions.

Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory demyelinating conditions primarily affecting the optic nerves and spinal cord. While NMOSD pathogenesis is mediated by aquaporin-4 antibody (AQP4-IgG) autoimmunity, increasing evidence suggests significant comorbidity with affective symptoms. The neuropathological mechanisms underlying this comorbidity, however, remain incompletely understood. We reported two cases of female patients with concurrent NMOSD and mood disorders that illustrate a shared neuroinflammatory etiology. Case 1, a 26-year-old female, presented with a decade-long history of mood instability, diagnosed as bipolar disorder (BD) mixed episode, which coincided with her NMOSD diagnosis. Case 2, a 25-year-old female, initially presented with major depressive disorder (MDD) but was subsequently diagnosed with NMOSD following the acute onset of neurological symptoms. Both patients were, serum AQP4-IgG positive and exhibited demyelinating changes in the frontal lobe. Following immunosuppressive and psychiatric treatment, both patients experienced marked improvement in neurological function, suicidality, and affective symptoms. These case reports suggest a bidirectional relationship between NMOSD and mood disorders, likely mediated by AQP4-IgG-driven neuroinflammatory responses. AQP4-IgG screening may serve as a critical tool to distinguish organic mood disorder from primary psychiatric conditions, particularly in patients with atypical neurological symptoms.

BACKGROUND:Patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose co-transporter 2 (SGLT2) inhibitors often have underlying conditions that predispose them to infection. While these agents offer cardiometabolic benefits, concerns persist regarding their impact on infectious risk. Existing literature has not comprehensively assessed their dose-dependent influence on severe infections such as sepsis. OBJECTIVES:To investigate the effect of GLP-1 receptor agonists and SGLT2 inhibitors on infection risk. DATA SOURCES:PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov up to December 18, 2024. STUDY ELIGIBILITY CRITERIA:Randomized controlled trials reporting target infection outcomes related to GLP-1 receptor agonists or SGLT2 inhibitor prescription. PARTICIPANTS:Individuals without evidence of ongoing infection at study initiation. INTERVENTIONS:GLP-1 receptor agonists or SGLT2 inhibitors. ASSESSMENT OF RISK OF BIAS:Cochrane risk of bias tool version 2.0. METHODS OF DATA SYNTHESIS:A frequentist random-effects model was used to assess the comparative incidence of infectious complications-classified as sepsis, abscess/gangrene, or other infections (e.g., pneumonia and urinary tract infection). Drop-out rates served to reflect acceptability. Sensitivity analyses included Bayesian modelling and subgroup analyses of diabetic status and treatment duration. RESULTS:Based on 105 randomized controlled trials with 219 283 participants, no significant association was found between GLP-1 receptor agonists or SGLT2 inhibitors and controls, except for high-dose canagliflozin (300 mg/day), which was the only intervention significantly associated with reduced sepsis risk versus control. This effect persisted in participants with diabetes. No significant associations were found between any other GLP-1 receptor agonist or SGLT2 inhibitor and risk of sepsis, abscess, gangrene, or other infections. Subgroup and meta-regression analyses confirmed robustness. Bayesian modelling yielded comparable results. Treatment duration had minimal influence on primary outcomes. CONCLUSIONS:This analysis identifies no significant evidence of infection-related adverse events related to GLP-1 receptor agonist or SGLT2 inhibitor prescription.

Objective While nutritional psychiatry offers a compelling evidence base for improving mental health outcomes, its translation into routine clinical care remains fragmented. This qualitative study explored how mental health practitioners in Australia and New Zealand perceive and integrate nutritional knowledge and practices into psychological care. Methods A qualitative study utilizing ten online focus groups and one online interview was conducted with 31 practitioners, including psychologists, counsellors, and social workers. Data were analysed using Kuckartz content analysis. Five overarching domains were identified: (i) knowledge, awareness, and confidence, (ii) practitioners’ experiences discussing nutrition with clients, (iii) drivers and barriers to implementation, (iv) scepticism and critical perspectives, and (v) future directions and perceived impact. Results While participants expressed strong motivation to deliver holistic, person-centred care, they were inhibited by systemic deficits, including lack of formal training, unclear professional scope, and insufficient system-level support. Regional contrasts revealed more flexible practice in New Zealand and greater regulatory caution in Australia. Conclusion Findings highlight widespread practitioner interest in nutritional psychiatry and underscore the need for structured education, clear ethical guidance, and interdisciplinary collaboration to embed nutrition within routine mental health care. Integrating dietetic expertise and evidence-based nutrition discussions into mental health services may enhance clinical practice implementation and client outcomes.

Neuroimmune dysregulation and altered pro- and anti-inflammatory signaling have been implicated in selected phenotypes of depressive and anxiety disorders. Interleukin-37 (IL-37), a member of the IL-1 family, exerts anti-inflammatory effects through extracellular signaling involving IL-18Rα and IL-1R8 and intracellular interactions with SMAD3. This scoping review mapped direct and indirect evidence concerning the relevance of IL-37 to depressive and anxiety disorders. PubMed/MEDLINE was searched through 12 July 2026, supplemented by backward citation searching and reference-list checking; evidence was charted by study type, population or model, IL-37 assessment, principal findings, and level of psychiatric relevance. Thirty-two IL-37-related sources were included. Direct psychiatric evidence comprised one small cross-sectional human study and two rodent stress-model studies, in which IL-37 was assessed as one component of broader inflammatory profiles rather than as a prespecified primary biomarker or intervention target. The remaining evidence was derived from non-psychiatric inflammatory conditions, central nervous system disease models, or mechanistic studies. These findings provide hypothesis-generating biological context but do not establish psychiatric specificity, causality, biomarker validity, or therapeutic efficacy. IL-37 should therefore be considered an exploratory research variable requiring validation in well-characterized longitudinal psychiatric cohorts using standardized assays and integrated immune profiling.

Abstract Dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium–glucose cotransporter 2 (SGLT2) inhibitors are widely prescribed for their cardiometabolic benefits, yet their hematologic oncologic safety remains uncertain. Because hematologic malignancies are highly lethal and biologically heterogeneous, delineating drug-specific risks across histopathologic subtypes is clinically crucial. This histopathology-stratified network meta-analysis (NMA) evaluated and compared the hematologic malignancy risks associated with individual agents from these drug classes. Following Cochrane guidance for adverse-event synthesis, we conducted this frequentist-based NMA of randomized controlled trials (RCTs). The primary endpoint was incident hematologic malignancy, categorized a priori into leukemia (acute and chronic forms), lymphoma (Hodgkin and non-Hodgkin), and myeloma/plasma cell neoplasms. Bayesian models were used as sensitivity analyses. Seventy-five RCTs including 270,471 participants were eligible. Dulaglutide was associated with a significantly increased risk of overall hematologic malignancy (RR = 2.17, 95% CIs = 1.14–4.17). In contrast, tirzepatide (RR = 0.22, 95% CIs = 0.06–0.78) and linagliptin (RR = 0.51, 95% CIs = 0.27–0.95) were linked to a reduced overall risk. In histopathology-specific analyses, tirzepatide showed a significant protective association against non-Hodgkin’s lymphoma, whereas no agent demonstrated clear signals for leukemia or myeloma. In this histopathology-focused NMA, dulaglutide emerged as the only agent with a significantly elevated overall hematologic malignancy risk, whereas tirzepatide and linagliptin exhibited protective profiles. The lymphoma-specific benefit observed for tirzepatide underscores the value of histologic subclassification when evaluating oncologic safety of antidiabetic therapies and calls for targeted mechanistic and long-term outcome studies. Trial registration PROSPERO CRD420251151419. The study protocol was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical University (TSGHIRB E202516007).