Does Weight Gain Associated with Thiazolidinedione Use Negatively Affect Cardiometabolic Health?

Thiazolidinediones (TZDs) are oral anti-diabetic drugs that are peroxisome proliferator-activated receptor gamma (PPARγ) agonists and act as insulin sensitizers. The clinical efficacy and durability of the currently available TZDs in improving glycemic control are well established. However, TZDs cause weight gain, which has been thought to be a class effect of TZDs. TZD-associated weight gain may result mainly from increased fat mass and fluid retention and may be in part congruent to the mechanism of action of TZD. Increases in fat mass are almost exclusively limited to subcutaneous fat, while there are no effects or even decreases in visceral fat. Insulin resistance and cardiovascular risk associated with fat accumulation (obesity) depend on body fat distribution, with visceral fat associated with insulin resistance and a greater degree of risk than subcutaneous fat. Therefore, despite TZD-associated weight gain, TZDs are less likely to confer an increased risk of insulin resistance and cardiovascular complications. As patients with diabetes are younger and/or more obese in Korea, TZDs may be a cost-effective treatment option, offering a unique insulin-sensitizing action and good durability for the long-term management of type 2 diabetes.