Once-Weekly Subcutaneous Semaglutide Improves Fatty Liver Disease in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study

Abstract

Background. Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with type 2 diabetes (T2D). Semaglutide, a glucagon-like peptide 1 receptor agonist, may have a therapeutic role by targeting common mechanisms involved in the pathophysiology of T2D and NAFLD. The study aimed to assess the effectiveness of Semaglutide on NAFLD in patients with T2D. Methods. Forty-eight patients were treated with subcutaneous Semaglutide in add-on to metformin for 52 weeks. After the baseline visit (T0), follow-up was scheduled quarterly (T3, and T6) and then at 12 months of therapy (T12). During each visit, body composition was analyzed by phase-sensitive bio-impedance, and NAFLD was diagnosed and staged by Ultrasound (US) imaging. Surrogate biomarkers of NAFLD were also calculated and followed over time. Results. A significant decrease in anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and laboratory indices of hepatic steatosis was observed during treatment. Similarly, fat mass and visceral adipose tissue (VAT) decreased over time more than skeletal muscle and free-fat mass. US-assessed VAT thickness and the 12-point steatosis score also declined at T3 up to T12. Liver steatosis improved in most patients (70%), showing a reduction by at least one class in the semiquantitative US staging. Conclusion. Besides glucose control and body composition improvements, Semaglutide was effective in ameliorating the clinical appearance and severity of NAFLD in T2D patients.

Comparison of clinical efficacy and safety of weekly glucagon‐like peptide‐1 receptor agonists dulaglutide and semaglutide in Japanese patients with type 2 diabetes: Randomized, parallel‐group, multicentre, open‐label trial (COMING study)

“…[24][25][26][27][28] Both dulaglutide and semaglutide have been reported to improve fatty liver. 29,30 To the best of our knowledge, there are no prospective comparative reports on the effects of dulaglutide and semaglutide on liver fat percentage at doses approved in Japan. This study revealed that only semaglutide significantly increased the L/S ratio during the study period.…”

“…GLP‐1RA has been reported to have positive effect on NAFLD similar to pioglitazone and sodium‐glucose cotransporter 2 inhibitors 24–28 . Both dulaglutide and semaglutide have been reported to improve fatty liver 29,30 . To the best of our knowledge, there are no prospective comparative reports on the effects of dulaglutide and semaglutide on liver fat percentage at doses approved in Japan.…”

Phenotyping obesity: A focus on metabolically healthy obesity and metabolically unhealthy normal weight

“…[265][266][267] Furthermore, they have a positive impact on body composition through significant improvements in VAT, fat mass index (FMI), epicardial fat and hepatic steatosis, thus making them an appealing drug in the management of different obesity phenotypes. [268][269][270] FGF21 is also being proposed as a potential novel therapeutic modality, especially with regard to improving hepatic steatosis. 271,272 Bariatric surgery to date is still the most effective strategy for weight loss and weight loss maintenance.…”

“…Furthermore, studies have shown that GLP‐1 analogues also exert positive effects on the cardiovascular system through weight‐independent mechanisms, including improved vascular endothelial function, ischaemic conditioning and reduction in systemic inflammation 265–267 . Furthermore, they have a positive impact on body composition through significant improvements in VAT, fat mass index (FMI), epicardial fat and hepatic steatosis, thus making them an appealing drug in the management of different obesity phenotypes 268–270 . FGF21 is also being proposed as a potential novel therapeutic modality, especially with regard to improving hepatic steatosis 271,272 …”

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases

“…Besides, bariatric surgeries significantly reduced cardiovascular events and prolonged the overall survival of patients [11]. Newly, the development of semaglutide, a glucagon-like peptide-1 (GLP1) agonist, and tirzepatide, a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide, also known as gastric inhibitory polypeptide (GIP), revolutionized the treatment of obesity, with simultaneous protective effects on atherosclerotic cardiovascular disease and NAFLD [12,13,[17][18][19]. Interestingly, the newly published study by Jastreboff et al indicated that retatrutide, a triple agonist of GIP, GLP1, and glucagon receptor, led to greater achievement in the management of obesity with up to -24.2 % percentage change in body weight after 48 weeks of treatment [20].…”