The effect of thiazolidinediones on the liver: from hepatotoxicity to therapeutic effect

Thiazolidinediones (TDD) are a group of hypoglycemic drugs used for the treatment of type 2 diabetes mellitus (DM). TDD are synthetic ligands of PPAR-γ-receptors activated by the proliferator peroxisome. When TDD is combined with PPAR-γ-receptors, transcription of genes regulating carbohydrate and lipid metabolism is triggered. TDD has protective properties against pancreatic β-cells, as it reduces glucose and lipotoxicity. These drugs reduce insulin resistance, have a positive effect on fat metabolism. This effect makes it possible to use one of the representatives of the class in the treatment of non-alcoholic fatty liver disease (NAFLD), which is confirmed by clinical recommendations from different countries. Type 2 diabetes and NAFLD are diseases closely related to each other by common pathogenetic patterns. When combined, patients have a high risk of developing non-alcoholic steatohepatitis, cirrhosis of the liver and hepatocellular carcinoma, as well as worsening of the course of diabetes mellitus. For many years, drugs of the thiazolidinedione class remained in the shadows due to the negative experience of using specific representatives – hepatotoxic troglitazone and increasing the risk of cardiovascular complications of rosiglitazone. The representative of the pioglitazone class, which has many proven positive effects on the cardiovascular system, lipid metabolism and the course of NAFLD, remained forgotten. It is necessary to find out whether hepatotoxicity is actually a class-effect of TDD or a particular effect of specific drugs. A literary search for information for the period from 1982 to 2023 was carried out in PubMed electronic databases, Elibrary.ru. This article will consider: the historical development of the TDD class, research in the field of the effects of pioglitazone on the liver.