Abstract / Summary
Metabolic dysfunction–associated steatotic liver disease (MASLD) is highly prevalent in type 2 diabetes mellitus (T2DM), in which hyperglycemia and obesity act synergistically to drive hepatic fibrosis. The relative contribution of glycemic versus weight control to fibrosis risk is not well defined. This study investigated the effect of optimal glycemic and anthropometric control on the Fibrosis-4 (FIB-4) index in patients with T2DM and MASLD. In this single-arm clinical trial, 50 adults with T2DM and MASLD received a 24-week multifactorial intervention comprising lifestyle modification and optimization of glucose-lowering therapy, targeting an HbA1c below 7% and a body-weight reduction of 5% or more. Anthropometric, metabolic, and hepatic parameters and the FIB-4 index were assessed at baseline and at week 24. Independent predictors of the week-24 FIB-4 index were identified using multivariable linear regression. After 24 weeks, body weight, waist circumference, blood pressure, lipid profile, aminotransferases, and glycemic indices improved significantly (HbA1c 9.04% to 6.77%; all p < 0.001). The FIB-4 index decreased from 1.86 ± 0.70 to 1.35 ± 0.44 (mean change − 0.51; p < 0.001), the proportion of low-risk patients rose from 22.0% to 48.0%, and no patient remained in the high-risk category. Optimal glycemic control was achieved in 68% and optimal anthropometric control in 38% of participants. After adjustment for baseline FIB-4, optimal glycemic control was independently associated with a lower week-24 FIB-4 index (B = − 0.229; p = 0.021), whereas optimal anthropometric control was not (B = − 0.048; p = 0.562). A 24-week multifactorial metabolic intervention was associated with significant improvements in cardiometabolic risk factors, liver enzymes, and FIB-4–based fibrosis risk in patients with T2DM and MASLD. Achievement of optimal glycemic control, but not weight loss, was independently associated with lower FIB-4 values at follow-up. These findings suggest that glycemic optimization may represent an important and potentially independent determinant of fibrosis-risk reduction in T2DM-associated MASLD, although larger controlled studies with histological or elastography endpoints are needed to confirm these observations. www.irct.ir , IRCT20250506065618N1. Registered on July 17, 2025.