Therapy
The thyroid hormone drug eprotirome cuts LDL cholesterol by up to 31% and lowers Lp(a), a randomised trial of 98 patients (J Intern Med 2015)
Original title: Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome
This multicentre, randomised, placebo-controlled, double-blind trial tested eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia, randomised to 100 or 200 microg/day eprotirome or placebo for 12 weeks. Eprotirome reduced LDL cholesterol by 23% at 100 microg and 31% at 200 microg, compared with 2% for placebo (P<0.0001), with similar reductions in non-HDL cholesterol and apolipoprotein B, while HDL cholesterol and apoA-I were unchanged. Serum triglycerides and Lp(a) also fell considerably, particularly in patients with elevated baseline levels, without adverse effects on heart or bone, though liver enzymes rose modestly in most patients. The findings show liver-selective thyroid hormone receptor stimulation with eprotirome lowers atherogenic lipoproteins, including Lp(a), without extrahepatic side effects.
Original abstract
Background: Liver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia.
Methods: We performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200 μg day(-1) eprotirome or placebo for 12 weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures.
Results: Eprotirome treatment at 100 and 200 μg daily reduced serum LDL cholesterol levels by 23 ± 5% and 31 ± 4%, respectively, compared with 2 ± 6% for placebo (P < 0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients.
Conclusion: In hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.