Background: Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a common chronic liver condition with significant metabolic and cardiovascular implications. Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated hepatic benefits in diabetic populations, their role in non-diabetic individuals with NAFLD remains unclear. Objective: This meta-analysis aimed to evaluate the effects of SGLT2 inhibitors in non-diabetic NAFLD/MASLD patients. Methods: PubMed, Embase, and CENTRAL were searched up to May 2025 for randomized controlled trials (RCTs) comparing SGLT2i with placebo or other pharmacologic agents in non-diabetic adults with NAFLD. Primary outcomes included changes in hepatic function; secondary outcomes assessed anthropometric, metabolic, and imaging-based markers of hepatic steatosis and fibrosis. A random-effects model was applied to estimate pooled mean differences (MDs) and 95% confidence intervals (CIs). Results: Five RCTs comprising 273 non-diabetic patients (142 in the SGLT2i group) were included. SGLT2i significantly improved liver enzymes: AST (MD = -2.03; 95% CI: -3.24 to -0.82; p < 0.01), ALT (MD = -4.50; 95% CI: -6.89 to -2.10; p < 0.01), and GGT (MD = -4.12; 95% CI: -6.87 to -1.37; p < 0.01). Modest but significant reductions were also observed in body weight (MD = -3.24 kg), BMI (MD = -1.02 kg/m²), and waist circumference (MD = -3.12 cm). However, SGLT2i did not significantly affect triglycerides, HbA1c, fasting glucose, liver stiffness, CAP scores, or FIB-4 index. Conclusion: SGLT2i significantly improves liver enzyme levels and anthropometric markers in non-diabetic individuals with NAFLD/MASLD, suggesting potential therapeutic benefits. However, their effects on hepatic steatosis resolution and fibrosis progression remain inconclusive. Graphical

Background: Conduction system pacing (CSP) has emerged as an alternative to right ventricular pacing (RVP) for atrioventricular block (AVB) aiming to avoid ventricular dyssynchrony and adverse heart failure outcomes yet clinical adoption remains limited due to insufficient randomised evidence. Objectives: This study aimed to assess the clinical outcomes of CSP versus RVP in patients with AVB based exclusively on randomised controlled trials (RCTs). Methods: MEDLINE, Embase and Cochrane were searched from inception to October 2025. Clinical outcomes comparing CSP and RVP were analysed using HR, risk ratio (RR) and mean difference with 95% CIs. Heterogeneity was assessed with I ² and robustness tested by sensitivity analyses. Outcomes included heart failure hospitalisation (HFH), all-cause mortality (ACM), composite endpoint and key cardiac parameters. Results: Data from five RCTs involving 985 patients with AVB were analysed. In the pooled analysis, the composite endpoint is significantly improved in the intervention pacing (HR=0.54; 95% CI 0.31 to 0.95; p=0.03), similarly with markedly reduced risk for HFH (RR=0.30; 95% CI 0.17 to 0.54; p<0.0001). However, no significant difference was observed between CSP and RVP in ACM (RR=0.69; 95% CI 0.36 to 1.30; p=0.25). Secondary outcomes significantly favoured the CSP group, as the change in left ventricular ejection fraction (LVEF) was significantly increased (p=0.008) and the QRS duration was significantly shorter (p=0.002) compared with RVP. Conclusion: In patients with AVB, CSP provides enhanced cardiac and clinical benefit compared with RVP driven by reduced HFH, improved LVEF and shorter QRS, while evidence regarding its influence on overall mortality remains uncertain.

Aim: To evaluate the efficacy and safety of the fixed-dose combination of cagrilintide and semaglutide (CagriSema) compared with semaglutide, cagrilintide, or placebo in adults with overweight or obesity, integrating current evidence from randomized controlled trials Methods: We performed a systematic review and meta-analysis (PROSPERO CRD420251128528) of randomized controlled trials comparing CagriSema with semaglutide, cagrilintide, or placebo. The primary outcome was weight reduction (%, categorical thresholds). Secondary outcomes included glycemia, waist circumference, and safety profile. Results: Four RCTs (n=4,810) were included. CagriSema achieved greater weight loss than semaglutide (MD: -7.44%; 95% CI -10.44 to -4.44), cagrilintide (MD: -8.75%; 95% CI -9.89 to -7.62), and placebo (MD: -13.85%; 95% CI -20.61 to -7.09). The likelihood of ≥15% and ≥20% weight loss was 2-3-fold higher with CagriSema versus monotherapy. Waist circumference was significantly reduced with CagriSema compared with placebo (MD: -10.85 cm; 95% CI -15.85 to -5.86). No consistent differences in HbA1 were observed. Gastrointestinal adverse events were more frequent with CagriSema, and discontinuations were correspondingly higher in the combination therapy group. Conclusion: CagriSema provides superior and clinically meaningful weight loss compared with semaglutide, cagrilintide, and placebo, with incremental benefits across responder thresholds, albeit at the cost of increased gastrointestinal intolerance. (Figure [1](#fig-cap-0001))