Thyroid hormone analogues for the treatment of metabolic disorders: New potential for unmet clinical needs?

Timothy J. Shoemaker, Tatsuyoshi Kono, Cary N. Mariash, Carmella Evans-Molina

Research output: Contribution to journalReview article

27 Scopus citations

Abstract

Objective: To provide a comprehensive review of the discovery and development of selective thyroid hormone receptor agonists and provide a discussion of their use in hyperlipidemia, obesity, and type 2 diabetes mellitus. Methods: Preclinical and clinical English language literature from 1930 to present was reviewed and thematically summarized. Results: Human trials have shown that thyroid hormone receptor β (TRβ) agonists effectively lower low-density lipoprotein, triglycerides, apolipoprotein B, and lipoprotein(a) levels. In preclinical studies, TRβ agonists enhance reverse cholesterol transport and decrease atherosclerosis in selected models. While animal data suggest these drugs may have additional utility to modulate weight and improve glucose homeostasis, human studies have not shown similar results. Conclusion: TRβ agonists are a novel therapeutic class for lipid management. Their mechanism of action for lipid lowering is distinct from statin drugs, suggesting a strong possibility for synergistic effects with combined therapy. The long-term effects of these drugs on cardiovascular outcomes, however, are unknown. Recently, the development of the most promising agent in this class, eprotirome, was halted over toxicology concerns following long-term canine studies. Consequently, the future of contemporary TRβ agonists is unclear. The creation of a next generation of TRβ agonists that provide additional tissue specific effects or bind TRβ with even higher selectivity may lead to improved safety and efficacy and allow for their application to other metabolic disorders like obesity and type 2 diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)954-964
Number of pages11
JournalEndocrine Practice
Volume18
Issue number6
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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