GLP-1 receptor agonists and MASLD in diabetes: A promising path?

• Published in: Journal of diabetes and its complications Vol. 39; no. 7; p. 109041
• Main Authors: Pennisi, Grazia, Petta, Salvatore, Maggio, Viviana, Rizzo, Manfredi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2025; Elsevier Limited
• Subjects: Agonists; Atherosclerosis; Clinical trials; Diabetes; GLP-1 receptor agonists; Glucagon; Hormones; Insulin resistance; Liver cancer; Liver cirrhosis; Liver diseases; Metabolism; Obesity
• ISSN: 1056-8727; 1873-460X; 1873-460X
• DOI: 10.1016/j.jdiacomp.2025.109041

Furthermore, the use of GLP-1 agonists was found to significantly reduce the likelihood of fibrosis progression (OR = 0.105, 95%CI = 0.014–0.789, p = 0.028), with protective effects persisting even after adjusting for age, gender, blood sugar, and blood pressure (OR = 0.756, 95%CI: 0.013–0.746, p = 0.025). Some, but not all, GLP-1 receptor agonists have also shown over the years cardiovascular benefit, mostly due to a reduction of atherosclerotic cardiovascular diseases, 17 and it has been suggested that this is due to a direct anti-atherosclerotic effect in reducing atherogenic lipoproteins, such as small dense low-density lipoproteins (LDL). 18 Notably, subjects with MASLD and MASH have increasing accumulation of small, dense LDL when more severe forms of the hepatic alterations are present, 19 and this exposes such patients to higher cardiovascular risk, since small dense LDL are associated with both the formation and progression of atherosclerosis. 20 Despite the growing interest in GLP-1 receptor agonists for the treatment of MASLD, no final conclusions have been reached so far, although several studies suggest promising results, particularly regarding their protective effects against liver fibrosis progression.