AIMS:Adjunctive therapies to insulin for type 1 diabetes mellitus (T1DM), including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), may improve glycaemic control and reduce insulin requirements; however, safety concerns remain, particularly for diabetic ketoacidosis (DKA). MATERIALS AND METHODS:PubMed, Ovid MEDLINE, Embase, Web of Science, Scopus and the Cochrane Library through 26 September 2025. Data were pooled using a random-effects model. Risk of bias analyses were performed. RESULTS:Ninety studies met inclusion criteria. GLP-1RAs produced modest improvements in glycaemic control, lowering glycated haemoglobin (HbA1c) (-0.56%) and increasing time-in-range (TIR), while reducing total and basal daily insulin requirements, body weight (-3.6 kg) and body mass index (BMI) (-1.05 kg/m2). Severe hypoglycaemia and DKA were rare; gastrointestinal adverse effects were the most common adverse effects; renal and cardiovascular outcomes were neutral. SGLT2is significantly improved HbA1c (-0.38%), TIR (+8.6 pp), insulin requirements (-4.7 U/day), body weight (-2.5 kg) and BMI (-0.82 kg/m2). Severe hypoglycaemia was uncommon, while DKA risk was increased (risk ratios = 2.19, 95% confidence interval 1.16-4.17), primarily in predictable clinical settings. Renal parameters remained stable or improved, and cardiovascular events were infrequent. Across drug classes, mortality and hospitalisations were rare. CONCLUSIONS:Adjunctive GLP-1RAs and SGLT2is provide modest clinical improvements in adults with type 1 diabetes. These benefits must be balanced against class-specific safety concerns, especially the increased risk of DKA with SGLT2-based therapies. Larger, long-term trials are needed to define their optimal use in routine care.

Traumatic stress is a psychobiological response to an overwhelming life event that exceeds the individual's capacity to cope. Emerging evidence suggests that exposure to traumatic stress: whether or not it results in post-traumatic stress disorder (PTSD) is associated with increased cardiovascular risk. This study aimed to examine the relationship between trauma-related psychiatric symptoms and markers of endothelial and cardiac autonomic function. A list of potentially traumatic life events and the self-report PTSD Symptom Checklist-5 were administered to 132 adults. To evaluate the endothelial function, carotid intima media thickness (CIMT) and flow mediated dilatation were measured for all participants. Additionally, the Ewing test results, heart rate (HR), blood pressure, and biochemical parameters were collected. Those who reported at least 1 stressor event of traumatic scope (n = 48, 36%) were compared to those who did not (n = 84, 64%) alongside participants with and without a diagnosis of PTSD. Carotid intima media thickness (0.61 mm [0.32-0.82] vs 0.41 mm [0.28-0.69], P < .0005), systolic blood pressure (SBP) (125 mm Hg [109-130] vs 114 mm Hg [95-130], P < .0005), morning HR (81 bpm [61-96] vs 77 bpm [50-100], P = .042), serum C-reactive protein (CRP, 1.40 mg/L [0.30-5.30] vs 0.30 mg/L [0.30-4.10], P = .014) values were significantly increased in the traumatic stressor group compared to the non-stressor group. Flow mediated dilatation values (8% [4-16] vs 11% [4-23], P < .0005) were lower in the traumatic stressor group than the non-stressor group. Presence of traumatic stress was positively correlated with CIMT (R = 0.56, P < .0005), CRP (R = 0.22, P = .03), and SBP (R = 0.41, P < .0005). Presence of traumatic stress was negatively correlated with flow mediated dilatation (r = -0.35, P < .0005). According to the logistic regression analysis, SBP, CIMT, and flow mediated dilatation values were independently associated with traumatic stress. The Diagnostic and Statistical Manual of Mental Disorders-5 diagnosis of PTSD (n = 19, 14%) and PTSD symptom total scores (mean = 22.3, SD = 16.1) were, however, not associated with any of the assessed biological variables. Trauma exposure regardless of PTSD diagnosis was independently associated with early signs of vascular dysfunction and elevated cardiovascular risk markers (SBP, CIMT, and flow mediated dilatation). Morever, morning HR and serum CRP values were found significantly different between the participants with and without a history of traumatic stress. These findings underscore the need to consider trauma history in cardiovascular risk assessment, even in the absence of clinically diagnosed PTSD.

Chronic kidney disease (CKD) is a leading cause of premature death due to the loss of kidney function and development of kidney failure, and because of attendant major adverse cardiovascular events. High-sensitivity C-reactive protein (hsCRP), a biomarker of systemic inflammation, is associated with increased risks of cardiovascular events and CKD progression. CKD is characterized by a pro-inflammatory state with upregulation of inflammatory pathways and disruption of anti-inflammatory mechanisms. The resulting systemic inflammation, along with local tissue-based inflammatory mechanisms, are key contributors to kidney damage, atherosclerosis and cardiac dysfunction. As a result, a series of inflammatory pathways and mediators have emerged as potential therapeutic targets for CKD and its major cardiovascular complications. Investigational treatments that have targeted inflammation include inhibition of apoptosis signal-regulating kinase-1 (ASK1) by selonsertib, Janus kinase (JAK) 1/2 inhibition with baricitinib, protein kinase C-β (PKCβ) inhibition with ruboxistaurin, nuclear factor erythroid 2-related factor 2 (Nrf2) activation with bardoxolone, phosphodiesterase inhibition with pentoxifylline and monoclonal antibodies against IL-1β and IL-6. Furthermore, proven therapies for CKD, including renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid antagonists, possess anti-inflammatory properties that might contribute to their previously established clinical benefits.

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance.

BACKGROUND:Kidney transplant recipients with pre-existing atherosclerosis or coronary artery disease (CAD) have an increased risk of adverse post-transplant outcomes. However, the extent to which pre-transplant CAD influences mortality, cardiovascular events, and graft function remains unclear. This systematic review and meta-analysis aims to evaluate the impact of pre-existing CAD on all-cause mortality, post-transplant cardiovascular events, and graft failure in kidney transplant recipients. METHODS:A systematic literature search was conducted using PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE. Studies reporting outcomes in kidney transplant recipients with and without pre-existing CAD were included. The primary outcomes were all-cause mortality, major cardiovascular events, and graft failure post-transplantation. Risk estimates were pooled using a random-effects model, with heterogeneity assessed using the I² statistic. The study protocol was registered with PROSPERO (CRD42024600751). RESULTS:A total of 16 studies involving 112,416 kidney transplant recipients were included. Patients with pre-transplant CAD had a significantly higher risk of all-cause mortality compared to those without CAD (hazard ratio [HR] = 1.68, 95% confidence Interval [CI]: 1.38-2.06, P < .01), with high heterogeneity (I² = 60.0%). The risk of post-transplant cardiovascular events was also significantly increased in patients with CAD (HR = 2.78, 95% CI: 2.00-3.86, P < .01), with moderate heterogeneity (I² = 36.1%). Graft failure was more common in recipients with pre-transplant CAD, although the effect size was smaller (HR = 1.09, 95% CI: 1.03-1.16, P < .01), with no observed heterogeneity (I² = 0%). CONCLUSIONS:Pre-existing CAD in kidney transplant recipients is associated with a significantly increased risk of all-cause mortality and post-transplant cardiovascular events, as well as a modestly but significantly increased risk of graft failure. These findings stress the need for enhanced cardiovascular risk assessment and management strategies in transplant candidates with CAD to improve long-term outcomes.

BACKGROUND:Frailty is a state of vulnerability that emerges from cumulative, non-genetic influences acting across the life course. This review applies an exposome lens, integrating general external exposures, specific external exposures, and internal biologic processes. We aimed to synthesize how social, environmental, behavioural, clinical, and biological exposures contribute to frailty and identify clinically actionable prevention targets. METHODS:This structured narrative review synthesized epidemiological, clinical, environmental, and mechanistic evidence linking exposome-related exposures to frailty in older adults. Literature was identified through targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, supplemented by reference screening. Evidence was organized across exposome domains and narratively appraised according to study design, temporality, consistency, biological plausibility, and clinical relevance. RESULTS:Socioeconomic disadvantages, loneliness, and social isolation are consistently associated with higher frailty risk, whereas green and walkable environments may support healthier aging through mobility and social participation. Protective factors include specific high-quality dietary patterns and physical activity, whereas ultra-processed foods, sedentary behaviour, air pollution, climate stressors, infections, and selected chemical exposures are linked to adverse outcomes. Cardiometabolic, cardiorespiratory, and neurological vulnerability further connect external exposures with frailty progression. Internal pathways, including chronic inflammation, mitochondrial dysfunction, endocrine-metabolic dysregulation, gut microbiome dysbiosis, and epigenetic aging support plausible mechanistic pathways through which exposures may contribute to frailty. CONCLUSION:Exposome-informed frailty care should combine validated frailty assessment with brief screening for actionable risks, including social connection, diet, physical activity, pollution and temperature vulnerability, infection history, vaccination status, and chronic disease burden. Practical strategies include social prescribing, healthier dietary patterns (e.g., Mediterranean-style diets), physical activity in green and low-pollution spaces, seasonal health planning, vaccination, and cardiometabolic optimization.

BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin therapies produce substantial weight loss and cardiometabolic improvement, yet treatment discontinuation is common and associated with adverse metabolic consequences. AIMS:This review aims to synthesize current mechanistic and clinical evidence on metabolic trajectories following GLP-1RA discontinuation, identify predictors of relapse, and propose a multidisciplinary framework for post-treatment management. MATERIALS AND METHODS:We conducted a narrative review of evidence from randomized withdrawal trials (including STEP-1 extension, STEP-4, and SURMOUNT-4), systematic reviews, meta-analyses, and large real-world observational cohorts encompassing over 289,000 patients. RESULTS:Discontinuation is associated with substantial weight regain (60%-90% within one year) and parallel reversal of cardiometabolic benefits. Modelling studies suggest that glycaemic, blood pressure, and lipid parameters return to baseline within approximately 12 months, while HbA1c normalizes within 12-18 months. Early discontinuation (< 1 year) is associated with increased risks of coronary artery disease and heart failure compared with continued therapy. DISCUSSION:Weight recurrence reflects biological adaptations to weight loss, including reactivation of orexigenic pathways and adaptive thermogenesis. In the absence of validated tapering strategies, structured multidisciplinary transition approaches combining pharmacological, behavioral, and psychological interventions may mitigate post-discontinuation relapse. CONCLUSION:GLP-1RA discontinuation should be considered a high-risk clinical transition rather than a treatment endpoint. Structured follow-up and multidisciplinary management are essential to preserve long-term cardiometabolic benefits.

The frequency of heart failure and hyperuricemia is increasing worldwide. Hyperuricemia as a complication of heart failure is known to be an indicator of poor prognosis. However, no consensus exists on whether treating hyperuricemia as a complication of heart failure would alleviate symptoms or improve prognosis in patients with heart failure. There is insufficient evidence regarding whether treatment with uric acid-lowering agents can alleviate symptoms and improve prognosis in patients with heart failure. However, considering the prevention of gout, hypertension, and chronic kidney disease caused by hyperuricemia, if the serum uric acid level does not fall below 8 mg/dL with improvement in lifestyle habits, uric acid-lowering agents can be a treatment option. In an US cohort study comprising approximately 100,000 participants using Medicare data, less aggravation of heart failure was observed in patients who were administered febuxostat compared to allopurinol. Recent evidence further suggests that serum uric acid may reflect not only a biomarker of disease severity but also underlying xanthine oxidase activity and oxidative stress, which may be therapeutically targetable in selected subgroups of heart failure patients. Moreover, differential effects among uric acid-lowering agents raise the possibility that drug-specific properties, rather than uric acid reduction per se, may influence cardiovascular outcomes. In this review, we discuss clinical trials on hyperuricemia with heart failure and its treatment. Further large-scale, high-quality, prospective intervention studies on the efficacy of treating hyperuricemia as a complication of heart failure are required.

Blood pressure variability (BPV), fluctuations in blood pressure across beat-to-beat, 24-h, day-to-day, and visit-to-visit timescales, has emerged as a risk marker that is independent of mean blood pressure. Frailty, a multidimensional syndrome of diminished physiological reserve, shares core biology with BPV, including vascular aging, impaired baroreflex function, autonomic dysregulation, and chronic low-grade inflammation. This narrative review synthesizes mechanistic, epidemiologic, and clinical evidence linking BPV and frailty. Mechanistically, arterial stiffness and endothelial dysfunction attenuate baroreflex buffering and transmit excess pulsatile load, while autonomic imbalance and inflammaging destabilize hemodynamics, compromise cerebral autoregulation, and promote sarcopenia and functional decline. Across cohorts of community-dwelling older adults and high-risk groups (e.g., chronic kidney disease and hemodialysis), higher short- and long-term BPV correlates with prevalent frailty and predicts incident frailty, cognitive decline, falls, cardiovascular events, renal progression, and mortality, often with effect sizes on par with traditional risk factors. Ambulatory blood pressure monitoring best captures short-term and circadian variability (including nocturnal patterns), home monitoring informs day-to-day variability, and clinic series quantify visit-to-visit variability; average real variability appears particularly informative in older hypertensive populations. Clinically, incorporating BPV into assessment may refine frailty screening and risk stratification, revealing vulnerability that is not apparent from mean blood pressure alone. Therapeutic implications include prioritizing long-acting antihypertensive regimens that stabilize BPV, optimizing adherence and lifestyle (exercise, diet, stress reduction), and addressing metabolic and inflammatory drivers, while recognizing that interventional evidence targeting BPV per se remains limited. Key gaps include heterogeneous BPV metrics and frailty definitions, limited standardization of measurement protocols, and a paucity of trials testing whether reducing BPV improves functional outcomes. Future work should not only harmonize BPV phenotyping and frailty definitions, but also investigate whether stabilizing BPV translates into tangible improvements in functional status, falls, and survival. Incorporating digital health tools, such as continuous monitoring and AI-driven analytics, may facilitate early detection of hemodynamic instability and its integration into frailty care models.

Primary glomerulonephritis encompasses a diverse group of kidney diseases with variable clinical trajectories and outcomes. Accurate prognostic stratification is critical for guiding individualized management and improving long-term renal survival. This narrative review synthesizes current evidence on the prognostic value of histological grading systems, circulating and urinary biomarkers, and integrative risk prediction models across major primary glomerulonephritis subtypes, including IgA nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis. Emphasis is placed on the utility of established classification systems (e.g., Oxford, MEST-C, chronicity scores), emerging tissue and fluid biomarkers (e.g., PLA2R antibodies, complement components, cytokine profiles), and the validation of multivariable prognostic tools and nomograms. We highlight areas of convergence between histopathologic lesions and molecular markers, as well as the evolving role of machine learning in predictive modeling. Ultimately, combining morphological, biochemical, and algorithmic tools holds promise for precision risk assessment and treatment tailoring in primary glomerulonephritis.

Chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 or the presence of clinical, imaging, or histopathological features of kidney injury over a 3-month period, has been linked to several comorbidities including cardiovascular diseases, such as myocardial infarction, cerebrovascular diseases, renal artery stenosis and peripheral artery disease. A pro-inflammatory and pro-fibrotic state, together with the accumulation of uremic toxins and impaired calcium-phosphorus homeostasis leading to mineral and bone disorders, appear to constitute the underlying pathophysiology of peripheral artery disease in CKD patients. Despite such association and the deleterious effects of peripheral artery disease, the association between CKD and peripheral artery disease is generally underestimated in clinical practice, with physicians being less likely to initiate pharmacotherapy or offer interventional treatments to patients with CKD. Many therapeutic options, including lifestyle modifications, methods for cardiovascular risk reduction such as anti-platelet or lipid-lowering drugs, targeted pharmacotherapies, and endovascular or surgical interventions are available for the management of peripheral artery disease. However, the diagnostic and/or therapeutic process in CKD patients is not as straightforward as it is in the general population, with misleading outcomes and higher treatment-related complications. Aim of this narrative review was to discuss the epidemiology, risk factors, underlying pathophysiology, and diagnostic and therapeutic approaches toward peripheral artery disease in CKD patients.

BACKGROUND:Chronic kidney disease (CKD) is associated with a high burden of cardiovascular remodeling and increased risk of heart failure with preserved ejection fraction (HFpEF). However, the interpretation of natriuretic peptide-based HFpEF diagnostic remains challenging in CKD populations, where structural cardiac abnormalities and elevated NT-proBNP levels frequently coexist. METHODS:We conducted a cross-sectional study including ambulatory patients with CKD stages G3-G4 and NYHA II dyspnea. Clinical, metabolic, vascular, and echocardiographic assessments were performed. HFpEF was assessed using a modified HFA-PEFF-based approach derived from the ESC-recommended diagnostic algorithm. We evaluated the impact of NT-proBNP thresholds on HFpEF classification and explored the relationship between NT-proBNP, echocardiographic diastolic dysfunction, and structural cardiac abnormalities. RESULTS:The cohort displayed a high cardiometabolic burden (74.9%), and structural cardiac abnormalities were highly prevalent. Using a modified HFA-PEFF diagnostic algorithm, HFpEF was identified in 52.9% of patients. However, when the biomarker domain was excluded, 86.7% of patients remained within the intermediate-probability range. In an exploratory analysis, a cutoff of 700 pg/mL was identified as the cohort-adapted threshold with the best diagnostic balance and identified 19.8% patients as having HFpEF. CONCLUSIONS:Patients with CKD G3-G4 exhibited substantial structural and functional cardiovascular abnormalities despite no prior diagnosis of heart failure. HFpEF classification varied according to the NT-proBNP threshold applied, while NT-proBNP demonstrated limited discriminatory performance for echocardiographic diastolic dysfunction. These findings support the need for more refined and CKD-sensitive approaches for HFpEF characterization in this population.

Chronic kidney disease (CKD) is a major public health concern, closely linked to an increased risk of cardiovascular disease (CVD), which remains the leading cause of morbidity and mortality in this population. While traditional risk factors such as hypertension and diabetes are prevalent in CKD, disease-specific mechanisms-including chronic inflammation, oxidative stress, mineral disturbances and the accumulation of uraemic toxins-further amplify cardiovascular vulnerability. In CKD, both the abundance and molecular cargo of circulating extracellular vesicles (EVs) are altered, reflecting the underlying metabolic and inflammatory milieu. These EVs propagate endothelial dysfunction, vascular calcification, inflammation, thrombosis and cardiac remodelling by transferring bioactive molecules such as proteins and microRNAs to target cells. Emerging evidence suggests that EVs not only serve as biomarkers for early detection and risk stratification of CVD in CKD but may also represent novel therapeutic targets. Preclinical studies demonstrate the potential of stem cell-derived and engineered EVs to promote cardiac repair and modulate pathological signalling. However, translation into clinical practice requires rigorous standardization, safety validation and well-designed human trials. This review synthesizes current knowledge on the mechanisms by which EVs bridge renal dysfunction and cardiovascular pathology, discusses their utility as biomarkers and outlines a research agenda for harnessing their therapeutic potential in CKD-associated CVD.

Even though insulin therapy is the cornerstone of diabetes mellitus management, multiple daily injections are associated with poor adherence. Once-weekly basal insulin therapy has emerged as a novel therapeutic approach and is being evaluated in multiple ongoing clinical trials. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of once-weekly insulin efsitora therapy compared with once-daily basal insulin therapy in patients with type 1 or type 2 diabetes mellitus. Primary endpoints include glycemic control, assessed via HbA1c reduction, and hypoglycemia, classified as level 1 (54-69 mg/dL), level 2 (<54 mg/dl), or level 3 (any hypoglycemic episode characterized by altered mental and/or physical functioning requiring assistance). We have performed a systematic review and meta-analysis through an extensive literature search of major databases including Scopus, PubMed/Medline, and Cochrane databases, and have only included randomized controlled trials. We have included 5 randomized controlled trials comprising a total of 2,562 patients: 1,358 (53%) in the insulin efsitora arm and 1,204 (47%) in the insulin degludec arm. Our data show that insulin efsitora therapy achieved a similar HbA1c reduction overall (estimated treatment difference (ETD) 0.08%, 95% CI -0.01 to 0.17; I² = 42.6%), in patients with type 1 diabetes mellitus (ETD 0.10%, 95% CI -0.64-0.85; I² =24.0%) and in patients with type 2 diabetes mellitus (ETD 0.05%, 95% CI -0.25 - 0.26; I² = 38.1%) compared with insulin degludec therapy. Moreover, no statistically significant differences were identified in overall hypoglycemic events, level 2 or 3 hypoglycemic episodes, or nocturnal hypoglycemia, irrespective of diabetes mellitus subtype. Our meta-analysis shows no statistically significant difference between once-weekly insulin efsitora therapy and insulin degludec therapy in terms of glycemic control and hypoglycemic events.

American Scientific Societies (AHA/ACC and others) updated in 2025 the Guideline on High Blood Pressure following 2024 ESC and 2023 ESH updates from Europe. Guidelines mostly agree on who should receive pharmacotherapy and on a common target of systolic blood pressure (SBP <130 mmHg) and diastolic blood pressure (DBP) <80 mmHg for most, as well as on individualizing BP targets according to patient characteristics. However, they differ in nomenclature, pharmacotherapy for people at lower cardiovascular risk and aiming at SBP <120 mmHg. Overall, 2025 AHA/ACC supports pharmacotherapy earlier and achieving lower BP targets than other recent guidelines: it recommends (high CVD risk) or finds reasonable (not high CVD risk, if not corrected by lifestyle) initiating pharmacotherapy for hypertension, defined as SBP ≥130 mm Hg or DBP ≥80 mmHg. The recommended (high CVD risk) or reasonable (not high CVD risk) target is SBP at least <130 mmHg, with encouragement to achieve SBP <120 mmHg, and DBP <80 mmHg. However, 2024 ESC and 2023 ESH use alternative terms (high normal or elevated BP) for BP values (i.e., ≥130-139 or ≥80-89 mmHg) that require pharmacotherapy only in high-risk groups. Additionally, 2023 ESH recommends avoiding actively aiming for SBP <120 mmHg or DBP < 70 mmHg. 2024 KDIGO avoids the term hypertension and suggests a target SBP <120 mmHg for people with CKD. It would be desirable that guidelines converge on such key issues as nomenclature and therapeutic targets.

Background:Metabolic complications after kidney transplantation (KT) significantly affect graft and patient survival. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardio-renal benefits in the general population, but evidence in KT recipients remains limited. Methods:We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines (PROSPERO: CRD420251153352). PubMed, Scopus, Web of Science, Ovid MEDLINE, and Cochrane Library were searched up to September 2025 for studies evaluating GLP-1RA therapy in adult KT recipients. Random-effects models pooled outcomes for metabolic, renal, cardiovascular, and safety endpoints. Results:Seventeen studies (n = 54 680 KT recipients) were included. GLP-1RAs use significantly reduced all-cause mortality (HR 0.53, 95% CI 0.36-0.79, k = 4) and major adverse cardiovascular events (OR 0.55, 95% CI 0.47-0.66, k = 3). Estimated glomerular filtration rate (eGFR) remained stable at 3 months, improved at 6 months (+1.99 ml/min/1.73 m², 95% CI 0.52-3.47, k = 5) and 12 months (+2.24 ml/min/1.73 m², 95% CI 0.02-4.46, k = 6), and was preserved at 24 months. GLP-1RAs lowered HbA1c (MD -0.54%, 95% CI -0.89 to -0.19, k = 13) and body mass index (SMD -0.32, 95% CI -0.49 to -0.15, k = 12) from baseline, with parallel reductions in insulin requirement and urinary albumin excretion. Tacrolimus levels were unaffected at 6 months and modestly decreased at 1 year without compromising graft function. Adverse events were mainly mild gastrointestinal intolerance (10%-20%), with rare discontinuations and no increased risk of hypoglycemia, pancreatitis, or infections. Conclusion:GLP-1RAs are associated with improved glycemic control, weight, and cardiovascular outcomes, with no consistent signal of adverse effects on graft stability and immunosuppressive balance. GLP-1RA integration into individualized post-transplant care may be considered for patients with diabetes or metabolic syndrome, with close clinical monitoring.