Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: A pilot prospective, randomized, controlled study

Paul W Ladenson, M. McCarren, E. Morkin, R. G. Edson, Mei Chiung Shih, S. R. Warren, J. G. Barnhill, L. Churby, H. Thai, T. O'Brien, I. Anand, A. Warner, B. Hattler, M. Dunlap, J. Erikson, S. Goldman

Research output: Contribution to journalArticle

Abstract

Context: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. Design: Eighty-six patients (aged 66 ± 11 yr, mean ± SD) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. Results: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T3 and T4, buttherewere no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and lowdensity lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides andnochange in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. Conclusion: This investigation of DITPA actions demonstrated its efficacy in reducing body weight andlowering totalandlow-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.

Original languageEnglish (US)
Pages (from-to)1349-1354
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume95
Issue number3
DOIs
StatePublished - Mar 2010

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Lipoproteins
Body Mass Index
Body Weight
Acids
Serum
Bone
Placebos
Thyrotoxicosis
Bone Remodeling
Osteocalcin
Therapeutics
Hypothyroidism
Thyroid Hormones
Metabolism
HDL Cholesterol
Triglycerides
Heart Failure
Bone and Bones
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins : A pilot prospective, randomized, controlled study. / Ladenson, Paul W; McCarren, M.; Morkin, E.; Edson, R. G.; Shih, Mei Chiung; Warren, S. R.; Barnhill, J. G.; Churby, L.; Thai, H.; O'Brien, T.; Anand, I.; Warner, A.; Hattler, B.; Dunlap, M.; Erikson, J.; Goldman, S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 95, No. 3, 03.2010, p. 1349-1354.

Research output: Contribution to journalArticle

Ladenson, PW, McCarren, M, Morkin, E, Edson, RG, Shih, MC, Warren, SR, Barnhill, JG, Churby, L, Thai, H, O'Brien, T, Anand, I, Warner, A, Hattler, B, Dunlap, M, Erikson, J & Goldman, S 2010, 'Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: A pilot prospective, randomized, controlled study', Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 3, pp. 1349-1354. https://doi.org/10.1210/jc.2009-1209
Ladenson, Paul W ; McCarren, M. ; Morkin, E. ; Edson, R. G. ; Shih, Mei Chiung ; Warren, S. R. ; Barnhill, J. G. ; Churby, L. ; Thai, H. ; O'Brien, T. ; Anand, I. ; Warner, A. ; Hattler, B. ; Dunlap, M. ; Erikson, J. ; Goldman, S. / Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins : A pilot prospective, randomized, controlled study. In: Journal of Clinical Endocrinology and Metabolism. 2010 ; Vol. 95, No. 3. pp. 1349-1354.
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abstract = "Context: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. Design: Eighty-six patients (aged 66 ± 11 yr, mean ± SD) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. Results: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T3 and T4, buttherewere no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and lowdensity lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides andnochange in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. Conclusion: This investigation of DITPA actions demonstrated its efficacy in reducing body weight andlowering totalandlow-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.",
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T1 - Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins

T2 - A pilot prospective, randomized, controlled study

AU - Ladenson, Paul W

AU - McCarren, M.

AU - Morkin, E.

AU - Edson, R. G.

AU - Shih, Mei Chiung

AU - Warren, S. R.

AU - Barnhill, J. G.

AU - Churby, L.

AU - Thai, H.

AU - O'Brien, T.

AU - Anand, I.

AU - Warner, A.

AU - Hattler, B.

AU - Dunlap, M.

AU - Erikson, J.

AU - Goldman, S.

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N2 - Context: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. Design: Eighty-six patients (aged 66 ± 11 yr, mean ± SD) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. Results: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T3 and T4, buttherewere no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and lowdensity lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides andnochange in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. Conclusion: This investigation of DITPA actions demonstrated its efficacy in reducing body weight andlowering totalandlow-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.

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