Many people who take thiazolidinediones (TZDs) to help control their diabetes suffer the undesirable side effect of weight gain. These drugs, also called glitazones, work by increasing the body's sensitivity to insulin, helping the body to better use the insulin it produces and in many cases reducing the amount of insulin that patients must inject.

These drugs often cause weight gain, however, because they induce fat cells to divide and produce more fat cells. New fat cells are small to begin with and are very active metabolically, sucking up free fatty acids and storing them as triglycerides. This helps reduce HbA1c in the first few months. Over time, these patients lay down more and more fat cells which, when they fill up with triglycerides, result in steady and progressive weight gain.

A new study has found that the drugs act by boosting the activity of a key enzyme that encourages fat cells to remove fatty acids from the blood. Reducing excess fatty acids increases the body’s response to insulin. However, the excess fatty acids that are removed are then converted to triglycerides – the form in which fat is stored in the body. The researchers conclude that is the reason that TZDs can lead to weight gain.

Understanding this mechanism can help scientists develop ways to reduce the TZDs' side effect of weight gain while also enhancing their insulin-sensitizing effects.

Related information Treatment - Oral medications

Source:  Guan HP, Li Y, Valentin M, et al. A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nature Medicine, Sept. 23, 2002;10:1038/nm780. (Abs.)