Weight-Loss Devices Could Lock In Wins from GLP-1 Drugs

Christina had tried the dieting and exercise before. The weight always came down, then came back up again, especially after giving birth to her son in 2022.

She had hoped that a new class of weight-loss drugs might finally offer something different. Obesity treatments like Wegovy and Zepbound had just arrived, helping people lose weight with unprecedented ease. But the price of these GLP-1 drugs puts them out of reach. Christina’s health insurance would not cover the cost.

Desperate for another option, Christina signed up for a clinical trial that guaranteed several months of successful weight loss therapy and then the possibility of something more. (Christina, a Texas woman in her 50s, asked that her last name be withheld to protect her privacy regarding her weight loss treatment.)

That something extra was not another injection or pill, but a one-time procedure using a new medical device. And instead of targeting the stomach or brain, the study focused on the gut itself: rewiring how 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 medications. The goal is to ensure the benefits without the high costs, weekly injections or lingering side effects. And in 2026, the first company to develop such a device will likely seek approval to offer it to patients.

“We’re creating a new therapeutic area,” says Harith Rajagopalan, co-founder and chief executive officer of that company, Fractyl Health, based in Burlington, Massachusetts.

Reset Metabolism for Sustainable Weight Loss

You can think of these systems as a happy medium between medications and bariatric surgery. The endoscope is a thin, flexible tube equipped with a camera and a guide wire 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, reshaping the intestinal tissue and recalibrating its response to food without a single incision. The procedure takes about an hour and patients usually 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 poor diet. As diets high in sugar and fat bombard the duodenum, the lining becomes inflamed and its normal signaling pathways are distorted. Mucosal cells in the tissues grow abnormally and propagate these maladaptive changes, blocking a dysfunctional pattern that leads to food cravings, weight gain, and insulin resistance.

The Fractyl device overcomes these entrenched changes. It works by deliberately injuring tissue, using near-boiling water to burn diseased cells in the intestinal lining. A natural healing process then begins, producing a new layer of healthy tissue and restoring proper metabolic control.

“You see regrowth after about two weeks, and that continues until the lining looks pretty much normal,” says Alan Cherrington, a physiologist at Vanderbilt University School of Medicine who consults for Fractyl.

Preliminary results from the clinical trial Christina participated in, called the Remain-1 study, indicate that the procedure works as expected to stabilize weight after GLP-1 treatment. Three months after stopping Zepbound, study participants who underwent the Fractyl procedure generally kept their weight stable or continued to lose weight, while those who received dummy treatment saw the number on their scales steadily climb.

The results are “honestly better than I thought,” says one of the doctors leading the trial, Shelby Sullivan, a gastroenterologist and obesity medicine specialist at Dartmouth Hitchcock Medical Center in Lebanon, NH.

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. “Within six months,” she said, “we will absolutely know whether it works or not.” »

Next generation devices for obesity

If the six-month data demonstrates sustained weight maintenance (full trial results are expected in 2026), then Fractyl intends to seek regulatory approval to market what could become the first device specifically cleared for post-GLP-1 weight control.

But Fractyl is not the only one pursuing this therapeutic frontier. Endogenex, a company based in Plymouth, Minnesota, uses a flexible, stretchable circuit board to apply pulsed electric fields directly to the duodenal wall to burn problem cells. Meanwhile, TeCure, in South Korea, and Aqua Medical, in Pleasanton, California, use lasers and radio-frequency heated water vapor, respectively, to achieve similar remodeling of the intestinal lining.

“Ultimately, they’re different methods of doing the same thing,” says Pichamol Jirapinyo, a bariatric endoscopist at Brigham and Women’s Hospital in Boston and co-founder of Bariendo, a network of 10 nonsurgical weight-loss clinics across the United States. While ongoing trials may clarify differences in effectiveness and safety, Jirapinyo (who consults for Fractyl) expects operational characteristics such as ease of use and procedure duration to play a decisive role in determining adoption by practitioners.

The timing of market entry is also crucial, and Fractyl, now leading the pack, is expected to provide the first large-scale clinical results. These results, from the Sullivan-led trial, could set the tone for an entire class of new device-based obesity treatments aimed at preserving the gains of GLP-1 drugs, notes Stacey Pugh, CEO of Endogenex. “If they succeed, it will explode the field of possibilities,” she said.

Alternative post-GLP-1 devices

Not everyone is convinced that resurfacing the duodenum is the way to go. In Europe, last year saw the arrival of a new weight loss device called Reset which, although not explicitly permitted for use in a post-GLP-1 treatment setting, introduces a sleeve-like lining into the duodenum that physically prevents contact between food and the intestinal wall. This device, however, is due to be removed within a year, offering only a temporary solution.

Other endoscopic approaches target the stomach: one, commonly used today, applies sutures to bend the stomach and reduce its size, while another, more experimental method burns the 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, says Andrew Storm, a therapeutic endoscopist at Wake Forest University in Winston-Salem, North Carolina. “The duodenum is paper-thin, compared to the stomach, which is like a thick neoprene bag,” he says.

Fractyl’s regulatory approval would allow the company to directly promote its product for post-GLP-1 weight maintenance, something Boston Scientific, maker of the most widely used stomach suturing device, is not legally allowed to do unless it engages in a new round of clinical trials. And this distinction could give duodenal therapies a marketing advantage. But Storm, who consults for Boston Scientific and was also involved in trials of the Endogenex system, raises concerns about the complexity of duodenal therapy. “It just introduces a whole new level of difficulty for the endoscopist that I think will impact scalability,” he says.

Holding on to hard-earned progress

For patients like Christina, the debate between the stomach and the duodenum, or between one company’s device and another’s, is largely academic. What matters to her is that the 50 kilos she lost with Zepbound, almost 20% of her body weight, have remained so far, a stability she attributes to the Fractyl device. Since the trial is randomized and blinded, it is possible that she actually underwent the sham procedure. But Christina is pretty sure she got the real thing.

Her reasoning comes from small but telling moments, like when her husband cooked burnt bits of smoked pork, sending out the kind of rich aromas that once would have sent her straight to the table. “It smelled really good, but I had no desire to eat 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 requires more than anecdotes. With pivotal trial results on the horizon, the coming year could determine whether these devices remain hopeful prototypes or become validated tools in the next era of obesity care.