Thiazolidinedione

The thiazolidinediones /θaɪ.əˌzoʊlɪdiːnˈdaɪ.oʊn/, abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone,[1] are a class of heterocyclic compounds consisting of a five-membered C3NS ring.

[3] As a result, cells become more dependent on the oxidation of carbohydrates, more specifically glucose, in order to yield energy for other cellular processes.

[4] The activated PPAR/RXR heterodimer binds to peroxisome proliferator hormone response elements upstream of target genes in complex with a number of coactivators such as nuclear receptor coactivator 1 and CREB binding protein, this causes upregulation of genes (for a full list see PPARγ): TZDs also increase the synthesis of certain proteins involved in fat and glucose metabolism, which reduces levels of certain types of lipids, and circulating free fatty acids.

Nonetheless, rosiglitazone, a certain glitazone, was suspended from allowed use by medical authorities in Europe, as it has been linked to an increased risk of heart attack and stroke.

[citation needed] The main side effect of all thiazolidinediones is water retention, leading to edema, generally a problem in less than 5% of individuals, but a big problem for some and potentially, with significant water retention, leading to a decompensation of potentially previously unrecognized heart failure.

[23] The new recommendations were largely based on the reasoning that prior meta-analyses leading to the original restrictions were not designed to assess cardiac outcomes and, thus, not uniformly collected or adjudicated.

The authors of the same analysis recommended that other blood sugar lowering agents be considered in people with other risk factors for bladder cancer such as cigarette smoking, family history, or exposure to certain forms of chemotherapy.