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Cited by 31Thyroid Disorders and TreatmentsDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Treatment and Management

The effect of a diiodothyronine mimetic on insulin sensitivity in male cardiometabolic patients: a double-blind randomized controlled trial

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van der Valk, Fleur, Hassing, Carlijne, Visser, Maartje, Thakkar, Purav, Mohanan, Anookh, Pathak, Kaushal, Dutt, Chaitanya, Chauthaiwale, Vijay +5 more·2014·PLoS ONE
DOI 10.1371/journal.pone.0086890PMC PMC3931609
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Abstract

BACKGROUND AND AIMS: Obesity and its associated cardiometabolic co-morbidities are increasing worldwide. Since thyroid hormone mimetics are capable of uncoupling the beneficial metabolic effects of thyroid hormones from their deleterious effects on heart, bone and muscle, this class of drug is considered as adjacent therapeutics to weight-lowering strategies. This study investigated the safety and efficacy of TRC150094, a thyroid hormone mimetic. MATERIALS AND METHODS: This 4-week, randomized, placebo-controlled, double-blind trial was conducted in India and The Netherlands. Forty subjects were randomized at a 1:1 ratio to receive either TRC150094 dosed at 50 mg or placebo once daily for 4 weeks. Hyperinsulinemic euglycemic clamp and (1)H-Magnetic Resonance Spectroscopy (MRS) were performed before and after treatment. RESULTS: At baseline, subjects were characterized by markedly impaired hepatic and peripheral insulin sensitivity. TRC150094 dosed 50 mg once daily was safe and well tolerated. Hepatic nor peripheral insulin sensitivity improved after TRC150094 treatment, expressed as the suppression of Endogenous Glucose Production from 59.5 to 62.1%; p = 0.477, and the rate of glucose disappearance from 28.8 to 26.4 µmol kg(-1)min(-1), p = 0.185. TRC150094 administration did not result in differences in fasting plasma free fatty acids from 0.51 to 0.51 mmol/L, p = 0.887 or in insulin-mediated suppression of lipolysis from 57 to 54%, p = 0.102. Also, intrahepatic triglyceride content was unaltered. CONCLUSION: Collectively, these data show that, in contrast to the potent metabolic effects in experimental models, TRC150094 at a dose of 50 mg daily does not improve the metabolic homeostasis in subjects at an increased cardiometabolic risk. Further studies are needed to evaluate whether TRC150094 has beneficial effects in patients with more severe metabolic derangement, such as overt diabetes mellitus and hypertriglyceridemia. TRIAL REGISTRATION: clinicaltrials.gov NCT01408667.

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Authors
van der Valk, F., Hassing, C., Visser, M., Thakkar, P., Mohanan, A., Pathak, K., Dutt, C., Chauthaiwale, V., Ackermans, M., Nederveen, A., Serlie, M., Nieuwdorp, M., & Stroes, E.
Affiliations
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Torrent Pharma (India) (IN)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-02-21
Volume
9
Issue
2
Pages
e86890
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0086890
PMC
PMC3931609
OpenAlex
W2037677271
Cited by
31
References
3
Citations by year
2025: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 3
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Pure Amsterdam UMC (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
insulin sensitivity, cardiometabolic risk, hepatic insulin sensitivity, endogenous glucose production, hyperinsulinemic-euglycemic clamp, 1H magnetic resonance spectroscopy, lipolysis, free fatty acids, intrahepatic triglyceride, obesity, drug safety and tolerability
MeSH terms
Adult, Diiodothyronines, Humans, India, Insulin Resistance, Male, Middle Aged, Netherlands, Magnetic Resonance Spectroscopy, Thyronines, Glucose Clamp Technique, Statistics, Nonparametric, Metabolic Syndrome

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