Thiazolidinediones: Not just for diabetes?

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The thiazolidinediones (a.k.a. “the glitazones”) are widely used in the treatment of of hyperglycemia. Although they have their side effects (an increased risk of cardiac events according to some epidemiologic studies, plus the possibility of fluid overload or liver problems), in the right patients they can be highly valuable in the control of blood sugars. They work by acting as ligands of PPAR-gamma, a transcription factor which when activated improves insulin sensitivity.

More recent studies, though it is still early, point to a possible role for TZDs in the treatment of renal disease, where it could potentially useful as an antifibrotic or an antiproteinuric agent. For instance, administration of rosiglitazone to diabetic rats results in an inhibition of mesangial cell proliferation (see here), and diabetic nephropathy human patients treated with TZDs also results in a decrease in albuminuria (see here for example). A recent study in last month’s CJASN describes a Phase I Trial (the FONT study) in which patients with FSGS were treated with rosiglitazone and the pharmacokinetics of this drug is described. All of these studies point to the possibility of non-insulin-mediated effects of this class of drug.

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