PCSK9 inhibitors improve lipid profile and hepatic steatosis surrogate indicators in patients with MAFLD and type 2 diabetes

Objective To investigate the impact of proprotein convertase subtilisin kexin type-9 inhibitor (PCSK9i) on patients with metabolic dysfunction-associated fatty liver disease (MAFLD) combined with type 2 diabetes mellitus (T2DM). Methods This retrospective study reviewed the clinical data of 60 inpatients with MAFLD combined with T2DM from the electronic medical record (EMR) system. According to the medical records, all patients were categorized into the Control group ( n = 30, atorvastatin 20 mg QN) and the PCSK9i group ( n = 30, evolocumab injection 140 mg Q2W in addition to atorvastatin). Body mass index (BMI), glycemic control, hepatic fibrosis and steatosis surrogate indicators such as aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), fatty liver index (FLI) and controlled attenuation parameter (CAP), and lipid profiles, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), were analyzed at baseline and the 12-week follow-up in both groups. Multivariable regression analyses for changes in hepatic fibrosis and steatosis surrogate indicators were performed. Results At the 12-week follow-up, both groups exhibited significant reductions in lipid levels, with the PCSK9i group demonstrating greater decreases in TC (48.65 vs. 23.32%) and LDL-C (25.84 vs. 21.09%) compared to the Control group ( P < 0.05). Meanwhile, the PCSK9i group exhibited significantly greater reductions in CAP (22.41 vs. 15.60%) and FLI (27.72 vs. 13.77%) in unadjusted analyses (both P < 0.05). Multivariable regression analyses demonstrated the superior improvement in CAP and FLI observed with PCSK9-i is independent of concomitant sodium-glucose co-transporter 2 inhibitor (SGLT-2i) therapy. Conclusion PCSK9i effectively reduced hepatic steatosis surrogate scores (FLI, CAP) and lipid levels (TC, LDL-C) in patients with MAFLD combined with T2DM.