Researchers report the first blinded, randomized, sham-controlled evidence that a procedure called duodenal mucosal resurfacing may offer a safe and lasting way to maintain weight loss without ongoing medication. The findings suggest it could help patients hold onto the benefits they achieved while taking drugs such as Ozempic or other GLP-1 therapies.

“As effective as GLP-1 medications are, many people stop taking them because of cost, side effects or simply not wanting to take a drug long-term,” said lead author Shelby Sullivan, MD, director of the Endoscopic Bariatric and Metabolic Program at Dartmouth Health Weight Center and professor of medicine, Dartmouth Geisel School of Medicine. “But, if they stop these medications, weight regain occurs in the vast majority of patients, and the metabolic benefits are lost. Finding a treatment that allows patients to stop these medications without weight regain or loss of metabolic benefit is a huge unmet need. These findings indicate that this minimally invasive procedure may provide lasting weight-loss maintenance.”

How the “Gut Reset” Procedure Works

Duodenal mucosal resurfacing is an investigational endoscopic treatment that uses controlled heat to remove damaged tissue from the inner lining of the duodenum, the first section of the small intestine just below the stomach. This process, which ablates (burns) the unhealthy mucosal layer, encourages the growth of new, healthier tissue.

The ongoing REMAIN-1 trial is designed to test whether this renewal of the intestinal lining can trigger a lasting metabolic reset, helping the body maintain weight loss after stopping medications like semaglutide or tirzepatide.

Trial Results Show Less Weight Regain

The current findings come from an early group of participants with six months of follow-up data. Among 45 people in this cohort, 29 received the resurfacing treatment while 16 underwent a sham procedure. All participants had previously lost at least 15% of their body weight using tirzepatide before stopping the drug.

On average, patients lost about 40 pounds while on GLP-1 therapy. Six months after discontinuing the medication, those in the control group regained significantly more weight. Participants who received the sham procedure regained about 40% more weight than those who underwent the actual treatment.

In addition, patients who had more extensive resurfacing regained only about 7 pounds and kept more than 80% of their weight loss. By comparison, the control group regained roughly twice as much. The gap between the two groups continued to widen from one to six months after the procedure, suggesting the benefits may persist and even strengthen over time.

“What’s particularly encouraging is that the benefit appears to increase over time rather than fade, and that it behaves like a drug in terms of dose response,” Dr. Sullivan said. “That gives us confidence that we’re targeting the right biology.”

Safety and Recovery

No serious complications were reported from either the device or the procedure. Recovery is relatively quick, with most patients returning to normal activities within about a day.

“Other than recovering from the general anesthesia, there isn’t much recovery time involved,” Dr. Sullivan said. “You can be back to your daily routine in about a day. Participants could not tell if they had the sham or real procedure because there are not a lot of symptoms after the procedure.”

Why the Gut Is Key to Weight Regulation

The treatment targets the small intestine, where many of the hormones affected by GLP-1 drugs are produced. Over time, diets high in fat and sugar can alter the lining of the duodenum, changing how the body processes food and regulates hormones. These changes can contribute to insulin resistance and metabolic disease.

By restoring a healthier mucosal layer, the procedure aims to reset how the body responds to food, helping stabilize metabolism at a lower body weight after stopping medications like Ozempic.

What Comes Next

Duodenal mucosal resurfacing is still considered investigational. The larger REMAIN-1 study includes more than 300 participants and is fully enrolled and randomized. Researchers expect topline six-month data from the pivotal cohort in early fourth quarter of 2026, followed by a planned marketing submission later that year.

Dr. Sullivan will present the findings from the study, “Duodenal mucosal resurfacing prevents weight regain after tirzepatide withdrawal: REMAIN-1 multicenter, randomized, double-blind, sham-controlled clinical trial — midpoint cohort results,” abstract 642, at 8:30 a.m. CDT, Monday, May 4.

The research team, led by the University of Cambridge, developed a modified version of hafnium oxide that functions as a highly stable, low-energy ‘memristor’ — a component designed to replicate how neurons connect and communicate in the brain. Their findings were published in the journal Science Advances.

Why Current AI Systems Use So Much Energy

Modern AI relies on traditional computer chips that constantly move data between memory and processing units. This back-and-forth transfer requires large amounts of electricity, and demand continues to rise as AI becomes more widely used across industries.

Neuromorphic computing offers a different approach. Instead of separating memory and processing, it combines both in one place, similar to how the brain works. This method could cut energy use by as much as 70% while also allowing systems to learn and adapt more naturally.

“Energy consumption is one of the key challenges in current AI hardware,” said lead author Dr. Babak Bakhit, from Cambridge’s Department of Materials Science and Metallurgy. “To address that, you need devices with extremely low currents, excellent stability, outstanding uniformity across switching cycles and devices, and the ability to switch between many distinct states.”

A New Approach to Memristor Design

Most existing memristors operate by forming tiny conductive filaments inside metal oxide materials. These filaments tend to behave unpredictably and often require high voltages, which limits their practicality for large-scale computing.

The Cambridge researchers took a different route. They engineered a hafnium-based thin film that switches states through a more controlled mechanism. By adding strontium and titanium and using a two-step growth process, they created small electronic gates, known as ‘p-n junctions’, at the interfaces between layers.

Instead of relying on filaments forming and breaking, the device changes its resistance by adjusting the energy barrier at these interfaces. This allows for smoother and more reliable switching.

Bakhit, who is also affiliated with Cambridge’s Department of Engineeirng, explained that this design solves a major issue in memristor development. “Filamentary devices suffer from random behavior,” he said. “But because our devices switch at the interface, they show outstanding uniformity from cycle to cycle and from device to device.”

Ultra-Low Power and Brain-Like Learning

Tests showed that the new devices operate at switching currents roughly a million times lower than some conventional oxide-based memristors. They can also achieve hundreds of stable conductance levels, which is essential for analogue ‘in-memory’ computing.

In laboratory experiments, the devices remained stable through tens of thousands of switching cycles and retained their programmed states for about a day. They also demonstrated key biological learning behaviors, including spike-timing dependent plasticity: the process that allows neurons to strengthen or weaken their connections based on timing.

“These are the properties you need if you want hardware that can learn and adapt, rather than just store bits,” said Bakhit.

Remaining Challenges and Future Potential

Despite the promising results, there are still obstacles to overcome. The current manufacturing process requires temperatures of around 700°C — higher than what standard semiconductor fabrication typically allows.

“This is currently the main challenge in our device fabrication process,” said Bakhit. “But we’re now working on ways to bring the temperature down to make it more compatible with standard industry processes.”

If this issue can be resolved, the technology could be integrated into practical chip-scale systems. “If we can reduce the temperature and put these devices onto a chip, it would be a major step forward,” he said.

Years of Trial and Error Behind the Breakthrough

The advance came after several years of experimentation and many setbacks. Bakhit said progress finally accelerated late last year when he modified the fabrication process, adding oxygen only after forming the first layer.

“I spent almost three years on this,” he said. “There were a huge number of failures. But at the end of November, we saw the first really good results. It’s still early days of course, but if we can solve the temperature issue, this technology could be game-changing because the energy consumption is so much lower and at the same time, the device performance is highly promising.”

The work was supported in part by the Swedish Research Council (VR), the Royal Academy of Engineering, the Royal Society, and UK Research and Innovation (UKRI). A patent application has been filed by Cambridge Enterprise, the University’s innovation arm.

Researchers at the University of California, Irvine are now exploring that possibility. Their latest study investigates a potential treatment aimed at slowing or even reversing “aging” in the eye, while also helping prevent conditions such as age-related macular degeneration (AMD).

“We show the potential for reversing age-related vision loss,” says Dorota Skowronska-Krawczyk, PhD, an associate professor in the Department of Physiology and Biophysics and the Department of Ophthalmology and Visual Sciences. The research involved collaborators from UC Irvine, the Polish Academy of Sciences, and the Health and Medical University in Potsdam, Germany. The findings were published in Science Translational Medicine in a paper titled “Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice.”

The ELOVL2 Gene and Aging Vision

This study builds on earlier research focused on Elongation of Very Long Chain Fatty Acids Protein 2 (ELOVL2), a gene widely recognized as a marker of aging. “We showed that we have lower vision when this ELOVL2 enzyme isn’t active,” says Skowronska-Krawczyk, who is also affiliated with the Robert M. Brunson Center for Translational Vision Research at the UC Irvine School of Medicine.

In that earlier work, increasing ELOVL2 activity in older mice raised levels of the omega−3 fatty acid docosahexaenoic acid (DHA) in the eye and improved visual function.

The newer study aimed to find a way to achieve similar results without relying on the ELOVL2 enzyme itself.

Why Vision Declines With Age

As the body ages, changes in lipid metabolism reduce the levels of very-long-chain polyunsaturated fatty acids (VLC-PUFAs) in the retina. These molecules are essential for maintaining healthy vision. When their levels drop, vision can worsen, and the risk of AMD increases.

The ELOVL2 gene plays a central role in producing both VLC-PUFAs and DHA, making it a key factor in how the eye ages.

Fatty Acid Therapy Restores Vision in Mice

To bypass the limitations of ELOVL2, researchers tested whether supplying the eye with the right fatty acids could help. They injected older mice with a specific polyunsaturated fatty acid and observed improved visual performance.

“It’s a proof-of-concept for turning lipid injection into a possible therapy,” says Skowronska-Krawczyk. “What is important is that we didn’t see the same effect with DHA.” Other studies have also raised questions about whether DHA alone can slow the progression of AMD.

“Our work really confirms the fact that DHA alone cannot do the work, but we have this other fatty acid that is seemingly working and improving vision in aged animals,” she says. “We have also shown on a molecular level that it actually reverses the aging features.”

Genetic Links to Macular Degeneration Risk

The researchers also identified genetic variants in the ELOVL2 enzyme that are associated with faster progression of AMD. “Now we actually have a genetic connection to the disease and its aging aspect,” says Skowronska-Krawczyk, “so we could potentially identify people at higher risk for vision loss progression.”

This discovery could lead to more targeted treatments and earlier interventions aimed at preventing serious vision decline.

A Promising Target for Anti-Aging Therapies

These findings strengthen the case for ELOVL2 as a major factor in aging. “I am pretty convinced it’s one of the top aging genes that we should look at when we think about anti-aging therapies,” says Skowronska-Krawczyk.

Beyond the Eye: Links to Immune Aging

The research may have broader implications beyond vision. In collaboration with scientists at UC San Diego, Skowronska-Krawczyk has also begun studying how lipid metabolism affects aging in the immune system.

That work found that a lack of ELOVL2 can speed up the aging of immune cells. It also suggests that lipid supplementation throughout the body could help counteract age-related changes in the immune system and may even play a role in blood cancers.

“Our first study explored a potential therapy to address vision loss,” says Skowronska-Krawczyk, “but with the information we’ve since learned about immune aging, we are hopeful the supplementation therapy will boost the immune system as well.”