Preliminary Results Show New Procedure Maintains Weight Loss After Discontinuing GLP-1 Medication

New data from the REMAIN-1 study of 1-month post glucagon-like peptide-1 (GLP-1) receptor agonist therapy show promising results, according to a news release from Fractyl Health.¹

Tirzepatide, Weight Loss, Weight Management | Image Credit: Cynthia | stock.adobe.com

“In obesity, people who stop taking GLP-1 drugs are at high risk of rapid weight and metabolic rebound, jeopardizing the hard-won clinical benefits achieved with the drugs initially. For this reason, the unmet need in obesity has shifted from achieving weight loss to achieving sustained maintenance of a lower weight,” Shailendra Singh, MD, director of bariatric endoscopy at West Virginia University, said in a news release.¹

In the preliminary data, the first patient achieved a 15% total body weight loss with tirzepatide (Mounjaro, Zepbound; Eli Lilly) in a 7-month period. After discontinuation, the patient underwent the Revita procedure to maintain their weight loss after 1-month post-procedure. The preliminary results showed that that the Revita procedure, an outpatient endoscopic procedure designed to modify duodenal dysfunction and restore metabolic health, could be a promising treatment option for long-term weight maintenance, according to the news release. Duodenal lining is a cause of obesity and type 2 diabetes, which makes it a promising target for the procedure. The data will be presented sometime in the first quarter of 2025.^1,2

In April 2024, the FDA approved the company's investigational device exemption regarding Revita’s efficacy to maintain weight lost post-discontinuation of GLP-1. The trial was a randomized, double-blind trial of the procedure compared with sham for patients who have lost at least 15% total body weight using tirzepatide. The investigators launched the study due to real-world data reporting high discontinuation rates and clinical trial data showing a risk of weight rebound after discontinuation. In prior clinical studies, data supported the procedure in its potential to maintain weight loss.²

“The unmet need in obesity is shifting from ‘How do we help people lose weight?’ to ‘How do we help people keep the weight off?’” Christopher Thompson, MD MSc, director of endoscopy at Brigham and Women’s Hospital and co-director for the center for weight management and wellness at Brigham Health, said in a news release. “We now need new therapeutic strategies that can offer durable weight maintenance, and I am excited for the prospect of the Remain-1 pivotal study to hopefully address this massive challenge in obesity today.”²

Investigators have included GLP-1–naïve patients with obesity and a body mass index of 30 kg/m². There will be at least 315 patients randomized 2:1 for treatment with Revita or sham. The study has generated significant interest, according to the company, and has over 100 patients enrolled across the first 8 clinical study sites less than 4 months after first site activation. The primary objectives of the study include Revita demonstrating superiority to sham in percent change in body weight from baseline to week 24 and demonstrating a majority of individuals receiving Revita maintaining clinically significant weight loss after discontinuation of therapy.^1,2

"We believe there is substantial clinical and economic value in new approaches to obesity that can enable durable weight maintenance after stopping GLP-1 based drugs," Harith Rajagopalan, MD, PhD, CEO of Fractyl Health, said in the news release. "We were very happy to work collaboratively with key advisors in obesity and gastrointestinal endoscopy by rapidly developing this protocol to address a huge, emergent unmet need in the field."²

REFERENCES

1. Fractyl Health Announces Positive Initial Clinical Results Demonstrating Weight Maintenance Following GLP-1 Discontinuation and Revita Procedure in First Patient of the REVEAL-1 Cohort. News release. Fractyl Health. January 13, 2024. Accessed January 13, 2025. https://ir.fractyl.com/news-releases/news-release-details/fractyl-health-announces-positive-initial-clinical-results

2. Fractyl Health Receives FDA IDE Approval for the Revita Remain-1 Pivotal Study of Weight Maintenance in Obesity after Discontinuation of GLP-1 Based Drugs. News release. Fractyl Health. April 1, 2024. Accessed January 13, 2025. https://ir.fractyl.com/news-releases/news-release-details/fractyl-health-receives-fda-ide-approval-revitar-remain-1