Introduction. Statins’ established cardiovascular benefits are often undermined by hepatic adverse effects in obese diabetic patients with suspected non-alcoholic fatty liver disease. We evaluated whether cannabis plant treatment is a safe and effective alternative to atorvastatin in a metabolically challenged rodent model. Methods. Fourteen obese and diabetic Wistar rats received either atorvastatin for 30 days or cannabis plant extract for 30 days. Main outcome: lipid profile; secondary outcomes: renal function, glycemia and endothelial health assessed through atherogenic indices. Safety was assessed using plasma liver enzyme concentrations. Results. Baseline biochemical profiles were similar between groups. Atorvastatin increased HDL-Col more than cannabis plant (MD: 44.3; IQR [33, 57.5] mg/dL, Hedges’ g 2.713 vs. MD: 14.3; IQR [14, 17] mg/dL, Hedges’ g 5.049), and cannabis plant did not change LDL-Col. Atherogenic index of plasma and Castelli Risk Index 1 improved with both interventions, more so with atorvastatin. Liver enzymes increased with atorvastatin (ALAT, MD: 15.9; IQR [12.5, 19.5] U/L; ASAT, MD: 33; IQR [26.5, 38] U/L) but remained virtually unchanged with cannabis. Serum creatinine increased with cannabis plant, with moderate effect size (Hedges’ g 0.798), but negligibly with statins (Hedges’ g 0.122). Conclusions. Cannabis plant extract modestly improved the lipid profile and atherogenic indices, with differences often not exceeding the change in control groups. Despite apparent liver safety, the undesired renal and neurological consequences limit applicability in humans. Further studies should prioritize addiction development and renal function.

Background/Objectives: To assess the impact of weight loss on the atherogenic profile of patients with obesity, we proposed the Atherogenic Central Load Index (ACLI). The aim of the study was to validate ACLI as a novel lipid biomarker reflecting the balance between atherogenic and antiatherogenic lipoproteins, the overall atherogenic burden, and its association with inflammatory markers. Methods: A prospective study was conducted from January 2024 to July 2024. A total of 73 adults with overweight or obesity completed a six-month dietary-based weight loss intervention. A 15% caloric deficit target was set, excluding the potential influence of pharmacotherapy, and limiting physical activity to daily walking. Statistical analysis focused on anthropometric measures, lipid panel parameters and derived atherosclerosis indices. Results: The intervention returned a median weight loss of 11.8 (IQR: 8–19) kg. Before–after analysis showed a statistically significant improvement in anthropometric indices and most lipid profile components. To assess the effect of weight loss on the atherogenic profile of patients, we proposed an atherogenic load index (Atherogenic Central Load Index (ACLI)). ACLI decreased significantly following the hypocaloric diet and showed a significant correlation with the inflammatory markers hs-CRP and IL-6. ACLI showed a strong, inversely significant correlation (p < 0.05) with AIP, hs-CRP and IL-6, at the time of intervention initiation and after 6 months. The evaluation of the obtained AUC values allowed to clearly highlight the superior discrimination performance of ACLI regarding the inflammatory markers hs-CRP and IL-6 in patients with overweight and obesity involved in dietary interventions for weight loss. Conclusions. The proposed index (ACLI) showed strong and significant associations with key inflammatory markers, including hs-CRP and IL-6. Moreover, ACLI demonstrated superior discriminatory performance for elevated inflammatory status in overweight and individuals with obesity undergoing dietary weight-loss interventions, outperforming traditional atherogenic indices related to atherosclerosis progression (AIP, CRI–1, and CRI–2). These findings support the potential clinical utility of ACLI as an integrative marker of atherogenic burden and cardiometabolic risk.