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: Obstructive sleep apnea (OSA) is strongly associated with obesity, and weight loss is a cornerstone of its management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are a class of medications that induce significant weight loss and have shown promise in improving OSA severity. Purpose: This meta-analysis aimed to evaluate the pooled efficacy of GLP-1 RAs on sleep-disordered breathing, body weight, and cardiovascular risk factors in patients with OSA. Methods: A systematic review and meta-analysis of four randomized controlled trials were performed, comparing GLP-1 RA therapy with placebo in adults with OSA. The primary outcomes analyzed were the mean differences in the change from baseline for the apnea-hypopnea index (AHI), body weight, and systolic and diastolic blood pressure. Results: In the pooled analysis, treatment with GLP-1 RAs was associated with a robust and statistically significant reduction in AHI (mean difference [MD]: -13.89 events/hour; p < 0.01). Therapy also resulted in substantial weight loss compared to placebo (MD: -12.46 kg; p < 0.01). For cardiovascular parameters, the use of GLP-1 RA was associated with a significant reduction in systolic blood pressure (mean difference [MD]: -4.86 mmHg; p < 0.01) and diastolic blood pressure ( p = 0.03). Conclusion: GLP-1 receptor agonists significantly reduce OSA severity, promote substantial weight loss, and lower systolic and diastolic blood pressure in patients with obstructive sleep apnea and obesity. These findings support the role of GLP-1 RAs as a multifaceted and effective therapeutic intervention for managing OSA.

Aims: The comparative effects of mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) remain uncertain, including potential differences between steroidal MRAs and finerenone. This Bayesian network meta-analysis aimed to compare the efficacy and safety of finerenone, eplerenone, and spironolactone vs placebo in HFpEF/HFmrEF. Methods: We searched Pubmed, Cochrane, and Embase for studies focused on MRA treatment in HFpEF and/or HFmrEF. Eight randomized controlled trials enrolling adults with HFpEF or HFmrEF (LVEF ≥40%) were analysed in a fixed-effects Bayesian network meta-analysis. Risk ratios (RRs) with 95% credible intervals (CrIs) were estimated for hospitalization for HF, cardiovascular death, and hyperkalaemia. Heterogeneity was assessed using I2. Results: Across a network comprising 10 644 patients, mean age 70.2; 48% women; mean LVEF 54.9%, finerenone reduced hospitalization for HF vs placebo (RR 0.84; 95% CrI 0.75–0.93), whereas spironolactone (RR 0.86; 95% CrI 0.73–1.01) and eplerenone (RR 0.86; 95% CrI 0.59–1.26) showed non-significant effects. None of the MRAs achieved a statistically significant reduction in cardiovascular mortality vs placebo: finerenone (RR 0.93; 95% CrI 0.78–1.10), spironolactone (RR 0.93; 95% CrI 0.76–1.14), and eplerenone (RR 1.10; 95% CrI 0.29–5.69). All MRAs increased hyperkalaemia vs placebo: finerenone (RR 2.06; 95% CrI 1.77–2.41), spironolactone (RR 2.13; 95% CrI 1.81–2.53), and eplerenone (RR 2.17; 95% CrI 0.75–7.97). Conclusion: In HFpEF/HFmrEF, finerenone was the only MRA to significantly reduce hospitalization for HF, while no agent significantly reduced cardiovascular mortality and hyperkalaemia risk increased across therapies. Overall, finerenone may offer the most favourable efficacy–safety balance among MRAs, pending confirmation in larger dedicated trials.