Randomized trial to evaluate mazdutide for T2DM and NAFLD in semaglutide-treated patients

Chinese patients with Type 2 Diabetes Mellitus (T2DM) frequently experience visceral fat accumulation and Metabolic Associated Fatty Liver Disease (MAFLD), significantly increasing cardiometabolic and all-cause mortality risks. The vicious cycle of hepatic lipid deposition and insulin resistance exacerbates T2DM progression. While GLP-1 receptor agonists (GLP-1RAs) like semaglutide are standard for T2DM, nearly a quarter of patients show poor response, and many still have persistent moderate-to-severe fatty liver despite treatment, indicating an unmet clinical need. Semaglutide lacks direct regulatory effects on adipose tissue and hepatic lipid metabolism, potentially leading to GLP-1 receptor desensitization with long-term use.

This multicenter, prospective, randomized controlled investigator-initiated trial (IIT) aims to evaluate the efficacy and safety of switching to mazdutide therapy. The study population comprises Chinese patients diagnosed with Type 2 Diabetes Mellitus (T2DM) and moderate-to-severe Nonalcoholic Fatty Liver Disease (NAFLD). All participants have previously been treated with semaglutide and have achieved glycemic control, yet they continue to exhibit persistent moderate-to-severe fatty liver. The trial's primary objective is to assess the clinical outcomes following this therapeutic switch.