Devices Target the Gut to Maintain Weight Loss from GLP-1 Drugs

Christina had tried dieting and exercise before. The weight always came off but then crept back on, especially after she gave birth to her son in 2022.She had hoped that a new class of weight-loss drugs might finally offer something different. Obesity treatments such as Wegovy and Zepbound had just arrived on the scene, helping people slim down with unprecedented ease. But the price tag of these GLP-1 drugs put them out of reach. Christina’s health insurance wouldn’t cover the cost.Desperate for another option, Christina enrolled in a clinical trial that guaranteed several months on a blockbuster weight-loss therapy—and then the possibility of something more. (Christina, a Texas woman in her early 50s, asked that her last name be withheld to protect her privacy about her weight-loss treatment.)This article is part of our special report Top Tech 2026.That something more wasn’t another injection or pill, but a one-time procedure using a new medical device. And instead of targeting the stomach or brain, it focused on the gut itself: rewiring how a part of the upper intestine, known as the duodenum, processes nutrients and regulates metabolism.Performed via a minimally invasive endoscopic device, this approach is designed to help people who want to stop taking GLP-1 drugs. The goal is to lock in the benefits without the high costs, weekly jabs, or lingering side effects. And in 2026, the first company to develop such a device is likely to seek clearance to bring it to patients.“We’re creating a new therapeutic area,” says Harith Rajagopalan, cofounder and chief executive of that company, Fractyl Health, based in Burlington, Mass.Resetting Metabolism for Lasting Weight Loss You can think of these systems as a middle ground between drugs and bariatric surgery. The endoscope is a slim, flexible tube equipped with a camera and a guidewire that leads a catheter into the digestive system. Doctors send the tools down the throat so they can view and modify the intestines from the inside—remodeling gut tissue and recalibrating its response to food without a single incision. The procedure takes about an hour or so, and patients typically go home the same day.To understand how the treatment works, it helps to first understand what goes wrong in the gut during years of unhealthy eating. As diets high in sugar and fat bombard the duodenum, the lining there becomes inflamed and its normal signaling pathways distorted. Mucosal cells in the tissue grow abnormally and propagate these maladaptive changes, locking in a dysfunctional pattern that drives cravings, weight gain, and insulin resistance.The Fractyl device overcomes these entrenched changes. It works by deliberately injuring the tissue, using near-boiling water to burn off diseased cells on the intestinal lining. A natural healing process then kicks in, producing a fresh layer of healthy tissue and re-establishing proper metabolic control.“You see regrowth at about two weeks, and it continues until the mucosa looks pretty normal,” says Alan Cherrington, a physiologist at Vanderbilt University School of Medicine who consults for Fractyl.Preliminary results from the clinical trial that Christina joined, termed the Remain-1 study, indicate that the procedure is working as intended to stabilize weight after GLP-1 therapy. Three months after stopping Zepbound, study participants who underwent the Fractyl procedure generally held their weight steady or continued to lose weight, while those who received a sham treatment saw the number on their scales climb steadily upward.The results are “honestly better than I thought they were going to be,” says one of the doctors leading the trial, Shelby Sullivan, a gastroenterologist and obesity-medicine specialist at the Dartmouth Hitchcock Medical Center in Lebanon, N.H.Sullivan cautions against drawing firm conclusions, given the small number of participants and short follow-up so far. But anyone watching the field won’t have to wait long for clearer answers. “By six months,” she says, “we absolutely will know if it’s working or not.”Next-Generation Devices for Obesity If the six-month data demonstrate lasting weight maintenance—full trial readouts are expected in 2026—Fractyl then intends to seek regulatory clearance to market what could become the first device specifically sanctioned for post-GLP-1 weight control.But Fractyl is hardly alone in pursuing this therapeutic frontier. Endogenex, a company based in Plymouth, Minn., is using a flexible, expandable circuit board to apply pulsed electric fields directly to the duodenal wall to burn away the problem cells. Meanwhile, TeCure, in South Korea, and Aqua Medical, in Pleasanton, Calif., are using lasers and radiofrequency-heated water vapor, respectively, to achieve a similar remodeling of the gut lining.“In the end, it’s different methods to do the same thing,” says Pichamol Jirapinyo, a bariatric endoscopist at Brigham and Women’s Hospital in Boston and a cofounder of Bariendo, a network of 10 nonsurgical weight-loss clinics across the United States. While ongoing trials may clarify differences in efficacy and safety, Jirapinyo (who consults for Fractyl) expects operational features such as ease of use and procedure time to play a decisive role in determining uptake among practitioners.Timing of market entry is critical, too—and Fractyl, now leading the pack, is expected to deliver the first large-scale clinical results. Those outcomes, from the trial that Sullivan is leading, could set the tone for an entire class of new device-based obesity treatments aiming to preserve the gains of GLP-1 drugs, notes Endogenex CEO Stacey Pugh. “If they are successful, it’s going to blow this field wide open,” she says.Alternative Post-GLP-1 Devices Not everyone is convinced that resurfacing the duodenum is the way to go. In Europe, the past year saw the arrival of a new weight-loss device called Reset that—while not explicitly authorized for use in a post-GLP-1 drug setting—introduces a sleevelike liner to the duodenum that physically prevents contact between food and the gut wall. That device must be removed within a year, however, offering only a temporary fix.Other endoscopic approaches target the stomach: One in common use today applies sutures to fold the stomach and shrink its size, while another, more experimental method burns off stomach tissue that regulates the secretion of appetite-stimulating hormones.These stomach-directed methods may offer a logistical advantage given the relative robustness and accessibility of the stomach, explains Andrew Storm, a therapeutic endoscopist at Wake Forest University in Winston-Salem, N.C. “The duodenum is paper thin, as compared to the stomach, which is like a thick neoprene bag,” he says.Regulatory clearance for Fractyl would allow the company to directly promote its product for post-GLP-1 weight maintenance—something that Boston Scientific, maker of the most widely used stomach-suturing device, is not legally permitted to do unless it engages in a new round of clinical trials. And that distinction could give duodenal therapies an edge in marketing. But Storm, who consults for Boston Scientific and has also participated in trials of the Endogenex system, raises concerns about the complexity of duodenal therapy. “It just introduces a whole other level of difficulty for the endoscopist that that I think will impact scalability,” he says.Holding On to Hard-Won Progress For patients like Christina, the debate over stomach versus duodenum, or one company’s device versus another’s, is largely academic. What matters for her is that the 50 pounds she lost on Zepbound—nearly 20 percent of her body weight—has stayed off so far, a stability that she attributes to the Fractyl device. Because the trial is randomized and blinded, it is possible she actually received the sham procedure. But Christina is fairly confident that she got the real thing.Her reasoning comes from small but telling moments, like when her husband was cooking smoked pork burnt ends, sending up the kind of rich aromas that once would have sent her straight to the table. “It smelled really good, but I didn’t have any desire to chow down on it,” Christina says.Experiences like Christina’s hint at the tantalizing promise of a lasting solution after drug-assisted weight loss, but medical-device development demands more than anecdotes. With pivotal trial readouts on the horizon, the year ahead could determine whether these devices remain hopeful prototypes or become validated tools in the next era of obesity care.