WVU Medicine has taken a leading role in a nationwide clinical trial investigating a novel endoscopic procedure that could help patients maintain their weight loss after discontinuing GLP-1 medications. The study addresses a critical challenge faced by users of popular weight loss drugs like Mounjaro and Wegovy, who often experience significant weight regain upon cessation of treatment.
Understanding the Weight Regain Challenge
Dr. Shailendra Singh, Director of Bariatric Endoscopy at WVU Medicine and principal investigator at the WVU site, explains that GLP-1 medications (including tirzepatide and semaglutide) work through multiple mechanisms. These drugs slow gastric emptying, suppress appetite through brain signaling, and enhance insulin production. However, when patients discontinue the medication, these effects reverse rapidly, leading to weight regain – often exceeding their initial weight loss within just four weeks.
"Once the medication is gone, all those factors are totally reversed. Now you have patients whose satiety or hunger was controlled. They don't have that inhibition anymore," explains Dr. Singh, highlighting the urgent need for alternative solutions.
The REMAIN-1 Trial and Revita DMR Procedure
The REMAIN-1 trial evaluates a procedure called Revita DMR (hydrothermal duodenal mucosal resurfacing), developed by Fractyl Health. The minimally invasive endoscopic procedure targets the duodenum, the initial section of the small intestine that plays a crucial role in appetite regulation and metabolic control.
During the procedure, physicians use an endoscope to deliver controlled hot water treatment to the duodenal lining, effectively ablating inflamed tissue. This process promotes regeneration of healthy tissue that may naturally produce beneficial hormones, including GLP-1.
"What we think is that over a period of time in diabetes, in patients with Type 2 diabetes or obesity or other factors, these cells [in the duodenum] are inflamed or hypertrophic which leads to the imbalance in the hormones," Dr. Singh elaborates.
Early Promise and Trial Progress
The current trial builds upon encouraging results from the REVEAL-1 study, where patients maintained their 15% weight loss four weeks post-procedure. REMAIN-1 has already enrolled over 100 patients across eight clinical sites within four months, demonstrating strong interest in this potential solution.
The randomized controlled trial design includes a 2:1 ratio of active treatment to sham procedure, ensuring scientific rigor in evaluating the procedure's effectiveness. Participants either must have already achieved significant weight loss or will use Zepbound to lose 15% of their body weight before undergoing the procedure.
Safety and Future Implications
The Revita DMR procedure is performed on an outpatient basis, with patients returning home the same day and resuming a normal healthy diet afterward. Dr. Singh emphasizes the importance of long-term follow-up, with plans to track outcomes at six and twelve months post-procedure.
Harith Rajagopalan, co-Founder and CEO of Fractyl Health, views the trial as a potential paradigm shift in metabolic disease treatment: "Revita represents a redefinition of how we approach metabolic disease treatment and raises the prospect of durably modifying the obesity epidemic without the need for burdensome drug therapy."
