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With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we present a 4-month case study in which the sustained, low-dose, and constant administration of the thyroid receptor β selective agonist GC-1 (sobetirome) from a novel nanochannel membrane implant was assessed in an obese, pre-diabetic rhesus macaque. Dramatic loss of white adipose tissue in the abdomen from 36 to 18% was observed via magnetic resonance imaging in conjunction with normalized serum insulin and glycemia, with no signs of cardiotoxicity shown. The non-human primate study highlights sustained low-dose delivery of GC-1 from our minimally invasive subcutaneous implant as a valuable approach to induce weight loss and manage obesity and comorbidities, including type 2 diabetes.

This study demonstrated a nanochannel membrane device (NMD) for controlled and sustained release of GC-1 in rats, in the context of the treatment of metabolic syndrome. Release profiles were established in vitro both with and without 5% labrasol for over 2 months. In vivo pharmacokinetic evaluation showed effective GC-1 plasma concentrations, which resulted in significant reductions in body weight after just one week of treatment when compared to the NMD releasing vehicle only (PBS). We also provided evidence that rats treated with NMD-GC-1 present sub-active thyroids and clear differences in the morphology of the epithelium and follicles as compared to the controls, while the heart showed changes in weight. Moreover, body temperatures remained stable throughout treatment, and glucose, pancreatic islet size, and liver histology appeared similar between the treated and control groups. Prolonged constant administration of GC-1 from the NMD proved to be a valid strategy to facilitate weight loss., (Copyright © 2017 Elsevier Inc. All rights reserved.)