Introduction: Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) have demonstrated cardiovascular and metabolic benefits individually; however, the comparative effectiveness of combination therapy versus monotherapy in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) remains incompletely characterized. Methods: We conducted three pairwise target trial emulations using the TriNetX Research Network. Adults with MASLD and T2DM initiating GLP‐1 RA plus SGLT2i combination therapy, GLP‐1 RA monotherapy, or SGLT2i monotherapy were identified. Primary outcomes were all‐cause mortality, major adverse cardiovascular events (MACE), and composite liver outcomes. Propensity score matching (PSM) (1:1) was performed for each pairwise comparison. Cox proportional hazards regression with Bayesian hierarchical bias‐effect (BHBE) correction was utilized to address residual confounding. Results: Following PSM, 42423 combination versus 42 423 GLP‐1 RA, 40349 combination versus 40 349 SGLT2i, and 51 826 GLP‐1 RA versus 51 826 SGLT2i patients were analyzed. Combination therapy significantly reduced all‐cause mortality versus SGLT2i monotherapy (hazard ratio [HR] 0.522, 95% confidence interval [CI] 0.488–0.559), with probable benefit after bias correction (corrected HR 0.655, posterior probability 92.4%; credible interval includes the null). Combination therapy demonstrated increased MACE risk versus GLP‐1 RA (HR 1.106, 95% CI 1.045–1.170), remaining significant after correction (corrected HR 1.111). Composite liver outcomes favored combination therapy versus SGLT2i (corrected HR 0.907, probability of benefit 81.9%). Conclusions: GLP‐1 RA and SGLT2i combination therapy significantly reduced mortality and liver outcomes versus SGLT2i monotherapy in MASLD with T2DM; however, increased MACE risk versus GLP‐1 RA monotherapy warrants consideration in management decisions.

Background/Objectives: Diabetic macular edema (DME) is a leading cause of vision loss in diabetic patients, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the standard management. However, treatment response varies significantly among patients, necessitating predictive tools. This systematic review and meta-analysis evaluated the diagnostic accuracy of artificial intelligence (AI) models in predicting anti-VEGF treatment response in DME patients. Methods: We conducted a dedicated literature review following PRISMA 2020 guidelines, searching PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases from inception up to 30 September 2025. Studies evaluating AI-based prediction models for anti-VEGF response in DME patients were included. The primary outcomes were sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). A bivariate random-effects meta-analysis was performed using available diagnostic accuracy data. Results: From 3107 participants across 18 studies, six studies with 427 participants provided complete diagnostic accuracy data for meta-analysis. The pooled sensitivity was 86.4% (95% CI: 82.1–90.1%) and the specificity was 77.6% (95% CI: 72.8–82.0%). The summary AUC was 0.89 with a diagnostic odds ratio of 22.0 (95% CI: 12.8–37.9). AI models demonstrated superior performance compared to other methods in 87.5% of comparative studies. Moderate heterogeneity was observed (I² = 45.2%). Conclusions: AI models demonstrate good diagnostic accuracy for predicting anti-VEGF treatment response in DME patients, with a promising role for improving personalized management strategies and improved outcomes.

Objective: Biologics for systemic lupus erythematosus (SLE) demonstrate variable treatment responses across trials. We evaluated baseline biomarkers as predictors of response to guide personalised therapy selection. Methods: We searched PubMed, OVID, Scopus, Cochrane and PsycInfo (January 2000–October 2025) for randomised controlled trials (RCTs) evaluating biologics (anti-BAFF, JAK inhibitors, anti-interferon, anti-IL-12/23, BTK inhibitors and T-cell modulators) in adult SLE patients. Primary outcomes included SLE Responder Index-4 response and time-to-flare. We performed random-effects meta-analysis stratified by interferon gene signature (IGS), serologic activity (anti-double-stranded DNA positivity and/or low complement) and high disease activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≥10), with false discovery rate correction for multiple comparisons. Results: Thirty-one RCTs (17 374 participants) were included. Overall, biologics improved SLE Responder Index-4 response versus control (risk ratio (RR) 1.26, 95% CI 1.19 to 1.33, p <0.0001). Serologically active disease showed the strongest predictive value (RR 1.45, 95% CI 1.28 to 1.63, p<0.0001, I²=0%, number needed to treat (NNT)=6.5). High baseline SLEDAI ≥10 also predicted response (RR 1.22, 95% CI 1.13 to 1.32, I²=0%). IGS showed non-significant trends (RR 1.39, 95% CI 0.97 to 2.00, p=0.074, I²=68.5%). Efficacy varied by mechanism, with anti-BAFF agents showing consistent benefit (RR 1.35, 95% CI 1.26 to 1.45). Biologics reduced serious adverse events (SAE) (RR 0.90, p=0.009); this should be interpreted considering lupus flares contribute to SAE counts. Individual non-disease adverse events showed expected patterns, with herpes zoster significantly increased (RR 1.19, p=0.017). Conclusion: Serologically active disease and high baseline disease activity significantly predict biologic therapy response with zero heterogeneity, while IGS showed inconsistent predictive value. These findings support using serological markers to guide biologic selection in real-world practice settings. Biologics demonstrate favourable safety profiles. PROSPERO registration number: CRD420251247531.

Background and Objectives: IgA nephropathy represents the most prevalent form of primary glomerulonephritis around the world, with significant heterogeneity in management strategies and outcomes. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological interventions for IgA nephropathy. Materials and Methods: We searched multiple databases through June 2025, identifying randomized controlled trials and observational studies evaluating pharmacological treatments in biopsy-proven IgA nephropathy. Primary outcomes included proteinuria reduction and estimated glomerular filtration ration (eGFR) preservation. Secondary outcomes included hard kidney endpoints and safety parameters. Random-effects meta-analyses were performed with comprehensive risk–benefit assessments. Results: Twenty-five studies were included. B-cell/plasma-cell-targeted therapies showed significant proteinuria reduction (−34.0% [95% CI: −45.7, −22.3%]), complement pathway inhibitors demonstrated superior eGFR preservation (+5.8 mL/min/1.73 m²/year [95% CI: 2.4, 9.2]). Systemic corticosteroids showed observed hard outcome benefits (HR 0.37 [95% CI: 0.26, 0.52]) but highest adverse event risk (RR 3.28 [95% CI: 2.11, 5.09]). Novel agents showed projected favorable effects (B-cell: HR 0.38; complement: HR 0.42) pending validation. Conclusions: Novel targeted therapies, especially B-cell/plasma-cell-targeted agents and complement pathway inhibitors, show promising risk–benefit profiles. However, longer-term data and standardized eGFR slope reporting are needed to confirm these findings compared to other immunosuppressive agents.

Introduction: Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have demonstrated significant weight‐reducing effects and may offer benefits in idiopathic intracranial hypertension (IIH); however, recent concerns about the risk of non‐arteritic anterior ischemic optic neuropathy (NAION) have emerged. Hence, this study was designed to examine the relationship between GLP‐1 RA use and optic outcomes in IIH patients. Methods: This study used the TriNetX Global Collaborative Network to perform a retrospective propensity score‐matched cohort study. It involved GLP‐1 RA exposure status to classify adult patients with IIH. Further, it applied propensity score matching (PSM) on demographics, comorbidities, and medications. In this study, the primary outcome was incident NAION; the secondary outcome was optic atrophy. Cox proportional hazards regression, time‐stratified analyses, and multiple testing corrections were performed. Results: From 144,678 IIH patients, 15,567 matched pairs were analyzed. GLP‐1 RA use demonstrated significantly decreased NAION risk (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24–0.93, p = 0.027) and optic atrophy risk (HR 0.78, 95% CI 0.64–0.94, p = 0.009). Time‐stratified analyses have demonstrated protective associations across all evaluated time windows. The optic atrophy finding remained significant after Bonferroni correction, while NAION remained significant after false discovery rate correction. Subgroup analysis revealed stronger protective associations in non‐diabetic patients (risk ratio 0.53, 95% CI 0.41–0.68) compared to diabetic patients (risk ratio 0.76, 95% CI 0.58–0.99). Conclusions: GLP‐1 RA utilization among IIH patients was associated with a reduced risk of NAION and optic atrophy. These findings align with the proposed pathway linking GLP‐1 RA‐induced weight reduction to lower intracranial pressure and papilledema reduction in IIH patients; residual confounding cannot be ruled out, and prospective studies are needed to confirm these associations.