Abstract: Thiazolidinediones (TZDs) are a group of insulin-sensitizing drugs that have primary application in the treatment of Type 2 Diabetes Mellitus (T2DM). By activating peroxisome proliferator-activated receptor gamma (PPARγ), TZDs increase insulin sensitivity in adipose tissue, skeletal muscle, and the liver, thereby optimizing glucose metabolism and lipid homeostasis. Their effectiveness in blood glucose control, however, is tempered by concerns about side effects such as weight gain, edema, cardiovascular risks, and increased bone fracture risk, and thus their sub-universal use. More recent studies on TZDs include the synthesis of novel derivatives with enhanced safety profiles, multi- or dual-targeting agents, and PPAR-γ- independent effects, aimed at minimizing side effects and preserving insulin-sensitizing activity. Additionally, personalized medicine strategies using genetic and biomarker-based approaches aim to optimize TZD therapy by aligning treatment with a patient's unique metabolic profile. TZDs outside diabetes also hold potential for the treatment of other diseases, such as nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. This review generally discusses the mechanisms, clinical uses, safety issues, and future perspectives on TZD research, explaining their evolving role in metabolic disease management. Future progress is destined to enhance their therapeutic utility through novel drug design and precision medicine strategies.
Pinki et al. (Wed,) studied this question.