Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) displays a worse prognosis in subjects with type 2 diabetes (T2D); effective treatments are, so far, scanty. High dose semaglutide showed efficacy in improving steatohepatitis. We longitudinally observed a MASLD cohort of T2D subjects starting semaglutide, to detect an improvement of non-invasive surrogates of steatosis and fibro-inflammatory liver involvement, evaluating the role of mild alcohol consumption. In 62 overweight/obese T2D with MASLD (36 teetotal and 26 mild alcohol consumers), anthropometric, biohumoral and transient elastography (TE) data were collected before (T0) and after an average time of 6.4 month (T1) from injective semaglutide prescription. Circulating levels of hormones (GIP, GLP-1, glucagon, insulin) and inflammatory markers (TNFα, MCP-1, IL-18, IL-10) were measured. Steatotic and fibro-inflammatory liver involvement was evaluated with FibroScan controlled attenuation parameter (CAP) and liver stiffness (LS), respectively. Significant (p<0.006) T0-T1 reductions of BMI (-1.4±0.2 kg/m2), waist circumference (-3±1 cm), fasting glucose (-40±6 mg/dl), and HbA1c (-12±1 mmol/mol) were observed. GOT (-10±3 UI/L), GPT (-18±5 UI/L), GGT (-33±15 UI/L), CAP (-25±8 dB/m, and LS (-0.8±0.4 kPa) were reduced, too. GLP-1 increased (+95.9 pM, p<0.0001) and IL-18 was reduced (-46.6 pg/ml, p=0.0002). At T1, CAP reduction was proportionate to BMI (r=0.388, p=0.0037) and to GLP-1 increase (r=-0.415, p=0.0251); no correlations were observed with glucose control or inflammatory markers variation. After adjustment for confounders, CAP improving was only related to GLP-1 increase (ß=-0.437, p=0.0122). Mild alcohol intake did not influence any of these parameters. Use of semaglutide in subjects with T2D and MASLD is associated with a significant decline of liver steatosis and fibro-inflammation proxies and IL-18 circulating levels; mild alcohol assumption did not exert any influence. An independent effect of GLP-1 raise was observed on reduction of steatosis, irrespective of alcohol consumption.