Thyromimetics: a journey from bench to bed-side

Abstract

Selective thyromimetics are synthetic analogs of thyroid hormones with tissue-specific thyroid hormone actions. Tissue selectivity is partly mediated by selectivity for the thyroid hormone receptor-β isoform, but is also enhanced by tissue-selective uptake. Several preclinical animal models and recent human clinical trials have provided sound evidence that thyromimetics can serve as pharmacological tools to improve serum lipids without affecting heart rate. Thyromimetics consistently and efficiently lowered low-density lipoprotein cholesterol and lipoprotein (a) plasma levels without positive chronotropic effects. Most importantly, thyromimetics had a synergistic action when used in addition to 3-hydroxy-3-methylglutaryl CoA reductase inhibitors. Animal data have further suggested that thyromimetics might be useful in the treatment of obesity, hepatic steatosis and atherosclerosis. However, only long-term phase III clinical trials will tell if the observed lipid lowering effects of thyromimetics will improve cardiovascular outcome in humans, too. At the moment, the treatment of dyslipidemia seems to be the major indication for the therapeutic use of thyromimetics, which are now rapidly moving from bench to bed-side.