Therapeutic Potential of Sodium-glucose Co-transporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists for Patients with Acute Coronary Syndrome: A Review of Clinical Evidence.

Atherosclerotic Cardiovascular Disease (ASCVD) is still one of the leading causes of death globally, with Coronary Artery Disease (CAD) being the most prevalent form of ASCVD. Patients with type 2 Diabetes Mellitus (DM) experience an increased risk for ASCVD during the disease course, with CAD being the most common cause of death among affected individuals, resulting in shorter life expectancy and increased morbidity among survivors. Recently, 2 novel classes of anti-diabetic drugs, namely Sodium-Glucose co-Transporter-2 (SGLT-2) inhibitors and Glucagon-Like Peptide-1 (GLP-1) receptor agonists, have shown impressive cardio-renal benefits for patients with type 2 DM, while they might decrease cardio-renal risk even in the absence of baseline DM. However, there is no evidence to date regarding their safety and efficacy in the setting of an acute coronary syndrome (ACS) event, regardless of concomitant DM. This study aims to provide a detailed, updated presentation of currently available clinical evidence concerning the potential role of SGLT-2 inhibitors and GLP-1 receptor agonists in the setting of an ACS, and to highlight whether those drug classes could be utilized as adjuncts to standard-of-care treatment in this specific patient population, along with a presentation of the potential short- and long-term cardiovascular benefits.

Mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a systematic review and network meta-analysis of 32 randomized trials.

INTRODUCTION: Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF. MATERIALS AND METHODS: MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Totally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]). CONCLUSIONS: MRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.

Diagnostic yield of implantable loop recorders: Results from the Hellenic registry.

AIMS: Implantable loop recorders (ILRs) are increasingly being used for long-term cardiac monitoring in different clinical settings. The aim of this study was to investigate the real-world performance of ILRs-including the time to diagnosis- in unselected patients with different ILR indications. METHODS AND RESULTS: In this multicenter, observational study, 871 patients with an indication of pre-syncope/syncope (61.9%), unexplained palpitations (10.4%), and atrial fibrillation (AF) detection with a history of cryptogenic stroke (CS) (27.7%) underwent ILR implantation. The median follow-up was 28.8 ± 12.9 months. In the presyncope/syncope group, 167 (31%) received a diagnosis established by the device. Kaplan-Meier estimates indicated that 16.9% of patients had a diagnosis at 6 months, and the proportion increased to 22.5% at 1 year. Of 91 patients with palpitations, 20 (22%) received a diagnosis based on the device. The diagnosis established at 12.2% of patients at 6 months, and the proportion increased to 13.3% at 1 year. Among 241 patients with CS, 47 (19.5%) were diagnosed with AF. The diagnostic yield of the device was 10.4% at 6 months and 12.4% at 1 year. In all cases, oral anticoagulation was initiated. Overall, ILR diagnosis altered the therapeutic strategy in 26.1% in presyncope/syncope group, 2.2% in palpitations group, and 3.7% in CS group in addition to oral anticoagulation initiation. CONCLUSIONS: In this real-world patient population, ILR determines diagnosis and initiates a new therapeutic management in nearly one fourth of patients. ILR implantation is valuable in the evaluation of patients with unexplained presyncope/syncope, CS and palpitations.

Bexagliflozin as an Adjunct Therapy to Diet and Exercise to Improve Glycaemic Control in Adults with Type 2 Diabetes.

Type 2 diabetes (T2D) is one of the leading causes of morbidity and mortality worldwide. Currently, over 10.5% of the adult population has been diagnosed with T2D, and almost 12% of total health expenditure is spent exclusively on T2D management globally. Sodium-glucose cotransporter-2 inhibitors are a relatively new class of oral antidiabetic agents that act by inhibiting renal sodium and glucose reabsorption. Except for their glucose-l owering effects, they have been associated with a more significant weight loss and blood pressure reduction and a lower risk of hypoglycaemia than other commonly prescribed antidiabetic drugs. On 20 January 2023, bexagliflozin became the fifth orally administered sodium-glucose transporter 2 inhibitor to be approved by the US Food and Drug Administration for the treatment of T2D as an adjunct therapy to diet and exercise in the USA after dapagliflozin, canagliflozin, empagliflozin and ertugliflozin. This review aims to discuss the current evidence on the efficacy and safety of bexagliflozin, which provides an important alternative treatment option for patients with T2D.

Vascular Alterations Following COVID-19 Infection: A Comprehensive Literature Review.

SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, has revealed a broader impact beyond the respiratory system, predominantly affecting the vascular system with various adverse manifestations. The infection induces endothelial dysfunction and immune system dysregulation, creating an inflammatory and hypercoagulable state. It affects both microvasculature and macrovasculature, leading to thromboembolic events, cardiovascular manifestations, impaired arterial stiffness, cerebrovascular complications, and nephropathy, as well as retinopathy-frequently observed in cases of severe illness. Evidence suggests that SARS-CoV-2 infection may result in persistent effects on the vascular system, identified as long-term COVID-19. This is characterized by prolonged inflammation, endotheliopathy, and an increased risk of vascular complications. Various imaging modalities, histopathological studies, and diagnostic tools such as video capillaroscopy and magnetic resonance imaging have been employed to visualize vascular alterations. This review aims to comprehensively summarize the evidence concerning short and long-term vascular alterations following COVID-19 infection, investigating their impact on patients' prognosis, and providing an overview of preventive strategies to mitigate associated vascular complications.

Intravenous Landiolol for Rate Control in Supraventricular Tachyarrhythmias in Patients with Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis.

Background: This systematic review explores the effects of landiolol administration in individuals presenting with supraventricular tachyarrhythmia (SVT) and concurrent left ventricular dysfunction, without being septic or in a peri-operative period. Methods: We systematically searched PubMed, Cochrane, Web of Science, and Scopus databases, retrieving a total of 15 eligible studies according to prespecified eligibility criteria. Results: Patients treated with landiolol experienced a substantial reduction in heart rate (HR) (mean HR reduction: 42 bpm, 95% confidence intervals (CIs): 37-47, I2 = 82%) and were more likely to achieve the target HR compared to those receiving alternative antiarrhythmic therapy (pooled odds ratio (OR): 5.37, 95% CIs: 2.87-10.05, I2 = 0%). Adverse events, primarily hypotension, occurred in 14.7% of patients receiving landiolol, but no significant difference was observed between the landiolol and alternative antiarrhythmic receiving groups (pooled OR: 1.02, 95% CI: 0.57-1.83, I2 = 0%). No significant difference was observed between the two groups concerning sinus rhythm restoration (pooled OR: 0.97, 95% CI: 0.25-3.78, I2 = 0%) and drug discontinuation due to adverse events (pooled OR: 5.09, 95% CI: 0.6-43.38, I2 = 0%). Conclusion: While further research is warranted, this systematic review highlights the potential benefits of landiolol administration in the management of SVTs in the context of left ventricular dysfunction.

The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF.

Effect of sodium-glucose cotransporter-2 inhibitors on continuous glucose monitoring metrics, as adjunctive to insulin in adults with type 1 diabetes mellitus: a meta-analysis of randomized controlled trials.

AIMS: This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on continuous glucose monitoring metrics as adjunctive to insulin in adults with type 1 diabetes mellitus (T1D). METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until October 25, 2023. Dual-independent study selection, data extraction and quality assessment were conducted. Results were summarized with random effects meta-analysis. RESULTS: Eight RCTs were identified, involving a total of 2310 T1D patients. The use of SGLT2is on top of standard insulin therapy was associated with a significantly higher time in range (TIR) compared to placebo (mean difference (MD) 9.7 %; 95 % confidence interval (CI) [8.3, 1.11]; P < 0.001). The time above range was significantly lower in patients receiving SGLT2is (MD -8.71 %; 95 % CI [-11.62, -5.79]; P < 0.001), whereas no difference was observed regarding the time below range (TBR) (MD 0.34 %; 95 % CI [-0.17, 0.85]; P = 0.19). A significantly lower sensor-recorded mean daily glucose was noted in the group receiving SGLT2is (MD -16.55 mg/dL; 95 % CI [-19.82, -13.29]; P < 0.001). When considering the metrics of glucose variability, SGLT2is demonstrated a significant favorable effect on the mean amplitude of glucose excursions (MD -16.92 mg/dL; 95 % CI [-25.31, -8.13]; P < 0.001) and the mean standard deviation of weekly glucose levels (MD -7.67 mg/dL; 95 % CI [-11, -4.35]; P < 0.001). No significant effect was observed concerning the coefficient of variation (MD -1 %; 95 % CI [-2.39, 0.4]; P = 0.16). Regarding safety outcomes, SGLT2is were significantly linked to higher odds of diabetic ketoacidosis compared to insulin alone (OR 3.18; 95 % CI [1.79, 5.66]; P < 0.001), with no significant impact on severe hypoglycemia events (OR 1; 95 % CI [0.54, 1.85]; P = 0.1). CONCLUSION: Our findings suggest that in individuals with T1D, adjunct therapy with SGLT2is provides a significant benefit in terms of TIR and reduced glucose variability, without an increase in TBR.

The Effect of Sodium-Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: This systematic review aimed to summarize the existing evidence from published randomized controlled trials (RCTs) on the impact of sodium-glucose cotransporter (SGLT) inhibitors on albuminuria levels and renal function in patients with type 1 diabetes mellitus (T1D). METHODS: The literature search was performed through Medline (via PubMed), Cochrane Library, and Scopus until November 11, 2023. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. RESULTS: In total, 5221 participants with T1D among 11 RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB 2). SGLT inhibitors were associated with a significantly greater reduction in urine albumin-to-creatinine ratio (UACR) compared to controls (MD = - 23.13%; 95% CI = [- 33.69, - 12.57]; P < 0.001; level of evidence high). On the basis of subgroup analysis, this effect was consistent across all available SGLT inhibitors, irrespective of the dosage. Finally, a neutral class effect was observed on the estimated glomerular filtration rate (eGFR, MD = - 1.03 mL/min/1.73 m2; 95% CI = [- 2.26, 0.19]; P = 0.1; level of evidence moderate). Only empagliflozin was associated with a significant reduction in eGFR compared to placebo (MD = - 2.23 mL/min/1.73 m2; 95% CI = [- 3.62, - 0.84]; P = 0.002). CONCLUSION: Our findings suggest that adjunctive therapy with SGLT inhibitors results in a significant reduction in albuminuria, while their use is associated with a neutral effect on creatinine clearance, as a measure of renal function. Future renal outcome trials are needed to assess SGLT inhibitors' role in the pharmacological armamentarium against diabetic nephropathy in T1D.

Risk of subclinical atherosclerosis in primary Sjogren's syndrome: A systematic review and meta-analysis.

BACKGROUND: Currently, the guidelines for prevention and management of atherosclerosis in patients with Sjogren's syndrome (SS) do not differentiate from those concerning the general population. OBJECTIVES: The present systematic review aimed to summarize evidence from primary studies assessing the risk of subclinical atherosclerosis in patients with primary SS (pSS). METHODS AND RESULTS: Literature was searched until June 2023. Eligible records were randomized controlled trials and observational studies comparing subclinical atherosclerosis markers between pSS patients and healthy controls. DerSimonian-Laird random effects models were used to calculate overall effect estimates. Totally, 19 observational studies comprising 1625 participants were included. Compared to healthy controls, pSS patients had significantly higher values of carotid-femoral intima-media thickness (cfIMT) (MD= 0.07 mm; 95 % CI= [0.04, 0.11]; p <0.001) and were more frequently diagnosed with atherosclerotic plaques (OR= 1.9; 95 % CI= [1.32, 2.74]; p <0.001). Moreover, pSS patients showed a decreased flow and nitrate-mediated dilation (MD = -2.48 %; 95 % CI= [-4.57, -0.39]; p = 0.02, MD= -2.11 %; 95 % CI= [-3.22, -1.01]; p <0.001, respectively). Similar results were observed for the pulse-wave velocity (MD= 0.7 m/s; 95 % CI= [0.36, 1.05]; p <0.001) and the ankle-brachial index (OR= 5.78; 95 % CI= [2.23, 14.99]; p = 0.003). Based on meta-regression analyses, only the disease duration and erythrocyte sedimentation rate were positively and significantly associated with higher cfIMT values. CONCLUSION: Patients with pSS have an increased risk of subclinical atherosclerosis compared to healthy population and thus possibly require early and disease-specific intervention. Further research is warranted for more accurate cardiovascular risk management in SS.

Residual leaks following percutaneous left atrial appendage occlusion and outcomes: a meta-analysis.

BACKGROUND AND AIMS: Residual leaks are not infrequent after left atrial appendage occlusion. However, there is still uncertainty regarding their prognostic implications. The aim of this study is to evaluate the impact of residual leaks after left atrial appendage occlusion. METHODS: A literature search was conducted until 19 February 2023. Residual leaks comprised peri-device leaks (PDLs) on transoesophageal echocardiography (TEE) or computed tomography (CT), as well as left atrial appendage patency on CT. Random-effects meta-analyses were performed to assess the clinical impact of residual leaks. RESULTS: Overall 48 eligible studies (44 non-randomized/observational and 4 randomized studies) including 61 666 patients with atrial fibrillation who underwent left atrial appendage occlusion were analysed. Peri-device leak by TEE was present in 26.1% of patients. Computed tomography-based left atrial appendage patency and PDL were present in 54.9% and 57.3% of patients, respectively. Transoesophageal echocardiography-based PDL (i.e. any reported PDL regardless of its size) was significantly associated with a higher risk of thromboembolism [pooled odds ratio (pOR) 2.04, 95% confidence interval (CI): 1.52-2.74], all-cause mortality (pOR 1.16, 95% CI: 1.08-1.24), and major bleeding (pOR 1.12, 95% CI: 1.03-1.22), compared with no reported PDL. A positive graded association between PDL size and risk of thromboembolism was noted across TEE cut-offs. For any PDL of >0, >1, >3, and >5 mm, the pORs for thromboembolism were 1.82 (95% CI: 1.35-2.47), 2.13 (95% CI: 1.04-4.35), 4.14 (95% CI: 2.07-8.27), and 4.44 (95% CI: 2.09-9.43), respectively, compared with either no PDL or PDL smaller than each cut-off. Neither left atrial appendage patency, nor PDL by CT was associated with thromboembolism (pOR 1.45 and 1.04, 95% CI: 0.84-2.50 and 0.52-2.07, respectively). CONCLUSIONS: Peri-device leak detected by TEE was associated with adverse events, primarily thromboembolism. Residual leaks detected by CT were more frequent but lacked prognostic significance.

Appraisal methods and outcomes of AMSTAR 2 assessments in overviews of systematic reviews of interventions in the cardiovascular field: A methodological study.

This study aimed to assess the methods and outcomes of The Measurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisals in overviews of reviews (overviews) of interventions in the cardiovascular field and identify factors that are associated with these outcomes. MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews were searched until November 2022. Eligible were overviews of cardiovascular interventions, analyzing systematic reviews (SRs) of randomized controlled trials (RCTs). Extracted data included characteristics of overviews and SRs and AMSTAR 2 appraisal methods and outcomes. Data were synthesized using descriptive statistics and logistic regression to explore potential associations between the characteristics of SRs and extracted AMSTAR 2 overall ratings ("High-Moderate" vs. "Low-Critically low"). The original results on individual AMSTAR 2 items were entered into the official AMSTAR 2 online tool and the recalculated overall confidence ratings were compared to those provided in overviews. All 34 overviews identified were published between 2019 and 2022. Rating of overall confidence following the algorithm suggested by AMSTAR 2 developers was noted in 74% of overviews. The 679 unique included SRs were mainly of "Critically low" (53%) or "Low" (18.7%) confidence and underperformed in items 2 (Protocol, no = 65.2%) and 7 (List of excluded studies, no = 84%). The following characteristics of SRs were significantly associated with higher overall ratings: Cochrane origin, pharmacological interventions, including exclusively RCTs, citation of methodological and reporting guidelines, protocol, absence of funding and publication after AMSTAR 2 release. Generally, overviews' authors tended to deviate from the original rating scheme and ascribe higher ratings to SRs compared to the official AMSTAR 2 online tool. Most SRs included in overviews of cardiovascular interventions have critically low or low confidence in their results. Overviews' authors should be more transparent about the methods used to derive the overall confidence in SRs.

Effectiveness and safety of injectable PCSK9 inhibitors in dyslipidaemias' treatment and cardiovascular disease prevention: An overview of 86 systematic reviews and a network metaanalysis.

OBJECTIVE: Multiple systematic reviews (SR) have been performed on the effects of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), often providing conflicting findings. This overview and network meta-analysis (NMA) aimed to summarize SR findings on the efficacy and safety of PCSK9i and provide an updated NMA. MATERIALS AND METHODS: MEDLINE (Pubmed), Scopus, Cochrane, Epistemonikos and Google Scholar were searched from inception to September 21, 2023 for SRs of randomized controlled trials (RCTs) and from January 1, 2020 to September 21, 2023 for additional RCTs. Double-independent study selection, data extraction and quality assessment were performed. Qualitative analysis was performed for SRs and a frequentist random-effects model NMA was performed for RCTs. RESULTS: Totally, 86 SRs and 76 RCTs were included. Alirocumab (77/86 [90%]) and evolocumab (73/86 [85%]) were mostly analyzed. Associations from SRs (35/42 [83%]) and the updated NMA indicated PCSK9i benefit on major adverse cardiovascular events (MACEs). Reductions were also noted for cerebrovascular events (47/66 [71%]), coronary revascularization (29/33 [88%]) and myocardial infarction (41/63 [65%]). Alirocumab was associated with reductions on all-cause mortality (RR=0.82, 95%CI [0.72,0.94]). Data on any CV event reduction were conflicting (7/16 [44%]). Inclisiran appeared effective only on MACEs (RR=0.76, 95%CI [0.61,0.94]). No reductions in heart failure were observed (0/16). No increases were identified between PCSK9i and any (0/35) or serious adverse events (0/52). However, PCSK9i were associated with injection-site reactions (20/28 [71%]). CONCLUSION: PCSK9i appeared to be effective in CV outcomes and their clinical application was generally safe.

High-resolution mapping of the circuit of typical atrioventricular nodal reentrant tachycardia.

BACKGROUND: Recent anatomic and electrophysiologic evidence has provided new insight into the anatomic substrate. Previous reports on electroanatomic mapping (EAM) of the circuit of atrioventricular nodal reentrant tachycardia (AVNRT) have been limited by mapping only the triangle of Koch on the right side of the septum and by the use of conventional mapping tools. The objectives are to obtain comprehensive high-resolution mapping of typical AVNRT and to investigate the role of the atrioventricular ring tissues in the circuit. METHODS: We employed EAM with the use of novel modules and algorithms for studying typical AVNRT from the right and the left sides of the septum. RESULTS: We performed extensive mapping of both the atrial septum and the septal vestibule of the tricuspid valve during typical AVNRT in 9 (6 females) patients, aged 49.6 ± 12.1 years. In two of these, left septal mapping was also obtained through the aorta. The earliest initial activation was variable, emanating from the superior or medial septum. The impulse consistently appeared below the orifice of the coronary sinus, at the site where its inferoanterior margin merged with the septal vestibule of the tricuspid valve at its entrance to the right atrium. It then returned to the initial activation site, presumably through the septal vestibular myocardium. The left septal activation area corresponded to that recorded on the right side. CONCLUSIONS: Typical AVNRT uses a circuit confined within the pyramid of Koch from the AV node to the septal isthmus, involving the myocardial walls of the pyramidal space.

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis.

AIM: The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis. RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2 ; 95% CI (-0.64, 1.42); p = .46; LoE moderate]. CONCLUSION: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.