“While GLP-1 receptor agonists facilitate weight loss by suppressing food intake, efficacy may be limited by metabolic adaptation, a counter regulatory process that lowers energy expenditure in response to weight loss. THR-β agonism, an orthogonal mechanism to GLP-1, appears to unlock additional efficacy of GLP-1 therapies by normalizing energy expenditure during weight loss, while preserving relative lean mass,” said
The poster and viewing detail are listed below:
Presentation Title: | TERN-501 Enhances Weight Loss Efficacy of a GLP-1R Agonist in Obese Mice via Increased Fat Mass Loss without Additional Loss of | |
Abstract Number: | 760 | |
Presentation Date and Time: | ||
Session: | Clinical Therapeutics—Incretin-Based Therapies | |
Presenter: |
The presentation reports results from a preclinical study in mice fed a high fat diet for 24 weeks prior to study start. Obese mice were treated once daily with vehicle, TERN-501, semaglutide, TERN-501+semaglutide, or tirzepatide for six weeks. The combination of TERN-501+ semaglutide significantly enhanced weight loss compared to semaglutide alone. Additionally, the TERN-501+semaglutide combination showed proportionally greater loss of fat mass relative to lean mass compared to semaglutide alone, indicating improved quality of weight loss.
The study also explored metabolic adaptation, a counter regulatory process that decreases energy expenditure and limits the magnitude and sustainability of weight loss. Mice treated with semaglutide and tirzepatide showed significant weight loss that was associated with decreases in energy expenditure. When TERN-501 was combined with semaglutide, weight loss-induced lowering of energy expenditure was prevented and increases in the thermogenesis marker, UCP-1, were observed in subcutaneous adipose tissue. TERN-501 has potential to attenuate metabolic adaptation and normalize energy expenditure, which may enhance the weight loss efficacy of GLP-1 therapies.
The full poster is available on Terns’ scientific publications website.
In addition, Terns announced that management will participate in a fireside chat at the Piper Sandler Virtual Obesity Day on
About TERN-501
TERN-501 is a THR-β agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β compared to other THR-β agonists in development. The Phase 2a DUET trial (NCT05415722) produced positive top-line data in
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