dbeard@dominionpost.com
MORGANTOWN – WVU Medicine is playing a lead role in a national clinical study of a minimally invasive surgical procedure for people who’ve lost weight through drugs like Mounjaro and fear regaining the weight when they go off the drugs.
Dr. Shailendra Singh is WVUM’s director of Bariatric Endoscopy and the WVU site’s principal investigator. He explained what they’re exploring.
Drugs such as Mounjaro and Zepbound (the generic name is tirzepatide) and Ozempic and Wegovy (semaglutide) are part of a drug class known as GLP-1s. GLP-1s are approved to treat Type-2 diabetes, but are also effective as weight-loss drugs.
But GLP-1 users may have to stay on them long-term to maintain their weight loss. Side effects and high costs pose barriers to long-term use, he said. And studies show that people who go off their GLP-1 therapy see a 3% weight gain within four weeks. Some gain more than what they lost.
Singh explained how GLP-1s work and why the weight comes back. They act in several areas. They slow the stomach down, which slows gastric emptying, meaning the food in the stomach for a longer time. They also act on the hunger center.
“That kind of changes your relationship to food. What people say is there’s not as much food noise and they can kind of avoid things which they were previously tempted to eat.”
They also increase insulin production and digestion.
“So once the medication is gone, all those factors are totally reversed. Now you have patients whose satiety or hunger was controlled. No they don’t have that inhibition anymore. So once that’s reversed, then people kind of tend to, obviously, eat. … So I think there’s a huge need that needs to be addressed here.”
The surgical procedure trial is called REMAIN-1 and builds on trials and practice of a procedure called Revita DMR, developed by Fractyl Health, a metabolic therapeutics company focused on approaches to the treatment of metabolic diseases, including obesity and Type 2 diabetes.
DMR is short for hydrothermal duodenal mucosal resurfacing. The duodenum is the first part of the small intestine, just beyond the stomach. Fractyl says it has an important role in regulating hunger and body weight. The duodenum is sensitive to the foods you eat and can signal to your brain to help the brain control your appetite.
Singh said, “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 [enlarged or thickened] which leads to the imbalance in the hormones.”
In the Revita procedure, an endoscope is inserted through the mouth down into the duodenum. Hot water is circulated into the duodenum to burn away the inflamed lining (called heat ablation). This allows regeneration of a new lining.
“And the idea is that the new lining that comes in is a healthy lining, which is secreting GLP-1s and other beneficial hormones,” Singh said.
The Revita DMR was developed to treat Type 2 diabetes and had positive results in improving blood glucose levels, liver insulin sensitivity, and other metabolic measures.
REMAIN-1 finds a new focus for the procedure: the potential to maintain weight loss. It builds on the experience of a prior trial, REVEAL-1. In REVEAL-1, four weeks after Singh’s first patient underwent Revita, none of the 15% of weight loss was regained. Further data will be forthcoming later this quarter.
REMAIN-1 is now recruiting patients, Singh said, who have either have lost weight or will take Zepbound to lose 15% of their body weight. When the desired weight loss is achieved, they will undergo the Revita DMR procedure. “So there’s a lot of interest, and we’re seeing very heavy interest.”
Fractyl said the REMAIN-1 study has enrolled more than 100 patients across the first eight clinical study sites in less than four months.
REMAIN-1 is a randomized controlled trial. Singh explained that for two patients who undergo the DMR procedure, a third will undergo what’s called a “sham” procedure where the endoscope is inserted but the lining is not burned away.
The randomization takes away the psychological component the patient may bring to the trial – any pre-existing biases regarding lifestyle modification or other matters – Singh said. It’s the next step beyond REVEAL-1 where all the patients underwent the DMR.
Singh said he expects it will take about a year to fully enroll all the patients for the trial. Then will come follow-up.
“I think that’s the important part is you want to follow these patients,” he said. “They might do well like our first, second patient [in REVEAL-1]. They did well for the first month. They did well for the second month. But what we want to see is what are the outcomes at six months? What are the outcomes at 12 months? So that’s when we might start getting some preliminary data.”
The endoscopy, he said, is a low-risk procedure, he said. Patients go home the same day. They then go on a regular healthy diet.
Harith Rajagopalan, co-Founder and CEO of Fractyl Health, said this about the REMAIN-1 trial: “As interest from key stakeholders continues to grow, we are increasingly confident in the transformative potential of our platform. Revita is more than a technological advancement – it 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. For the millions of people struggling with obesity, this marks an exciting step forward in providing accessible and enduring solutions.”
