An open-label, 48-week, randomized controlled trial depicted that in patients diagnosed with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), Tofogliflozin use alleviated liver histological alterations by increasing hepatic expression of genes engaged in fibrosis, inflammation, and energy metabolism. Yumie Takeshita et al. aimed to assess the efficacy of sulfonylureas and sodium-glucose cotransporter 2 (SGLT2) inhibitors in hepatic gene expression profiles and liver pathology in NAFLD and diabetes.

Overall, 40 patients with biopsy-verified NAFLD were randomized to take either 0.5 mg of Glimepiride or 20 mg of Tofogliflozin once a day. The percentage of patients whose individual scores for the histological categories of fibrosis, lobular inflammation, hepatocellular ballooning, and steatosis had improved by at least one point was the major endpoint. Hepatic gene expression patterns, metabolic indicators, and alterations in liver enzymes served as the secondary endpoints.

The Tofogliflozin group had an improvement in fibrosis scores (60%), but there was no discernible inter-group difference in the changes from baseline. The Tofogliflozin group exhibited significantly reduced lobular inflammation (50%), hepatocellular ballooning (55%), and steatosis (65%), while the Glimepiride group showed only improved hepatocellular ballooning (25%). The liver expression of genes implicated in energy metabolism, fibrosis, and inflammation was well correlated with liver histological alterations and rescued by tofogliflozin use.

Tofogliflozin was able to reverse histology-associated patterns in fibrosis, inflammation, and energy metabolism that were discovered by hepatic gene expression profiling. Hence, Tofogliflozin and Glimepiride improved metabolic function and liver histology in people with NAFLD and type 2 diabetes, with no clinically meaningful variation between the two drugs. More verification is required through longer and more extensive clinical studies of SGLT2 inhibitors.