TIXiMED Announces Promising Preclinical Data: Oral TIX100 Prevents Weight Regain After GLP-1 Cessation in Obesity Model

TIX100 prevented weight regain in mice after semaglutide discontinuation Supports potential role as oral weight maintenance therapy following GLP-1 Receptor Agonist (GLP-1) treatment, addressing a major challenge in long-term obesity management

TIXiMED, Inc., a clinical-stage pharmaceutical company developing a novel oral therapy targeting thioredoxin-interacting protein (TXNIP) for diabetes and metabolic disorders, is pleased to highlight new research by investigators at the University of Alabama at Birmingham (UAB) Comprehensive Diabetes Center. The study demonstrates that its oral compound, TIX100, effectively prevents weight rebound following discontinuation of GLP-1 treatment in a mouse model of diet-induced obesity.

In the study, mice treated with semaglutide experienced significant weight loss of over 13% body weight during a 2-week treatment period while continuing a high-fat diet. Upon discontinuation of semaglutide, untreated mice rapidly regained 14% of their body weight, mirroring the weight rebound frequently seen in patients who stop GLP-1s. In contrast, mice receiving oral TIX100 showed no significant regain and maintained their reduced body weight throughout the four-week post-GLP-1 period. Weight maintenance with TIX100 was linked to reduced fat mass, decreased food intake, and lower serum leptin levels, with no observed loss of lean mass. These findings are consistent with prior research showing that TIX100 limits high-fat diet-induced weight gain through improved leptin sensitivity and reduced food intake.

“Weight regain remains a major challenge after stopping GLP-1s, with many patients experiencing substantial rebound despite great initial weight loss success,” said Anath Shalev, MD, Founder, Chief Scientific Officer, and Chief Medical Officer of TIXiMED, and lead author of the study. “These preclinical results highlight the potential of TIX100 as an oral follow-on therapy addressing a critical unmet need, to help sustain weight loss without the side effects often associated with GLP-1s.”

“Stopping GLP-1-based therapy after weight loss is a fairly common occurrence, usually related to cost or side effects. Almost always, the weight lost is all regained within a year,” said John Buse, MD, PhD, Verne S. Caviness Distinguished Professor of Medicine at the North Carolina School of Medicine. “These preclinical findings are intriguing and, if the results translate in future human studies, TIX100 would address an important gap and certainly have a role in weight management programs,” Dr. Buse concluded.

“We are excited by these preclinical findings, suggesting TIX100 could help patients maintain weight loss following GLP-1 therapy discontinuation,” said Stephen Daly, CEO of TIXiMED. “This reinforces our belief in the broad potential of TIX100 in multiple disease states, and we are planning additional studies to build on these results,” Mr. Daly added.

TIX100 is a specific, orally available TXNIP inhibitor originally developed for its beta-cell protective effects in diabetes. It has received FDA Investigational New Drug approval in diabetes and demonstrated safety and tolerability as well as encouraging early metabolic signals in a Phase 1 trial in healthy subjects.

The current study, titled “Prevention of Weight Regain after GLP1RA Cessation with Oral TIX100,” was peer-reviewed and published in the current online issue of Diabetes, Obesity and Metabolism. While these results are promising, they are preclinical in nature, and human clinical trials will be required to confirm and validate the findings.

About TIXiMED, Inc.

TIXiMED is a clinical-stage pharmaceutical company dedicated to developing and commercializing a first-of-its-kind oral therapy for TXNIP inhibition. The company’s lead candidate, TIX100, targets underlying mechanisms of diabetes and metabolic disease to protect beta-cell function, improve glucose control, and address related metabolic conditions. TIXiMED is advancing TIX100 toward further clinical development for diabetes and metabolic indications. For more information, visit www.tiximed.com.

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