New Treatment Options for MASLD Patients with Type 2 Diabetes

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis in individuals with at least one cardiometabolic risk factor, most commonly type 2 diabetes mellitus (T2DM). People with non-alcoholic fatty liver disease, even without other metabolic factors, have a higher risk of T2DM. MASLD includes isolated liver steatosis, metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma. MASLD patients are also at a higher risk of developing T2DM than the general population. International guidelines recommend a stepwise approach for identifying those at high risk of fibrotic progression, using the FIB-4 index for initial screening, followed by transient elastography. The link between MASLD and T2DM is notable due to shared pathophysiological mechanisms, some of which are reversible with treatment used in T2DM. Many new glucose-lowering drugs have also proven effective in improving anthropometric and metabolic parameters, as well as the stage of hepatic steatosis and fibrosis. Recent evidence suggests that GLP-1RAs and SGLT2is have beneficial effects in MASLD patients with T2DM. Specifically, GLP-1RAs improve hepatic insulin signaling, modulate lipid metabolism, reduce inflammation, and decrease hepatocyte oxidative stress. European guidelines recommend resmetirom as a MASH-targeted therapy, if locally approved, for adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥ 2) and GLP-1RAs in MASH, including compensated cirrhosis, but they should be used for their respective indications, such as T2DM and obesity. Given the post-COVID burden of MASLD and its high risk of liver fibrosis progression among T2DM patients, this review specifically provides an overview of the complex relationship between MASLD and T2DM. Additionally, it examines current understanding of liver fibrosis evaluation and the effects of novel treatment options, with a particular focus on glucose-lowering therapies and their effects on necroinflammation, hepatic fat accumulation, and fibrosis progression in patients with MASLD and T2DM.