GFMA: A New Era in Non‑Surgical Weight Loss
Obesity is a chronic, lifelong disease that often resists diet and exercise alone. Bariatric surgery has been the gold standard for substantial weight loss, but many patients are reluctant to undergo an operation. What if an endoscopic procedure could curb hunger and achieve surgical-level weight loss – all without any incisions? Recent studies (the ABLATE I and ABLATE II trials) suggest this may be possible. These trials explored a novel technique called gastric fundus mucosal ablation (GFMA), especially in combination with endoscopic sleeve gastroplasty (ESG), and the results are very promising. Patients experienced significant weight loss, dramatic reductions in hunger hormones, and improved appetite control – approaching outcomes seen with surgical sleeve gastrectomy, but via a scar-free outpatient procedure. Below, we break down the findings and what they mean for the future of weight loss treatment.
What is GFMA and How Does It Work?
GFMA is an endoscopic procedure that burns the inner lining of the stomach’s fundus (the upper pouch of the stomach) in a controlled manner. This might sound intense, but it’s done from inside the stomach using a flexible endoscope and specialized tools – no external cuts required. The fundus is a key player in appetite: its mucosa produces about 80–90% of the body’s ghrelin, the so-called “hunger hormone,” and the fundus also expands to accommodate food and signal fullness. By ablating (destroying) the fundal mucosa, GFMA directly targets hunger at its source.
Illustration: An endoscopic probe (black tube) delivers thermal energy to ablate the gastric fundus mucosa (dashed outline). This controlled burn destroys ghrelin-producing cells in the fundus, reducing hunger signals without surgery. A fluid cushion is injected under the mucosa to protect deeper layers, then the tissue is heated to induce ablation. As the area heals, scar tissue forms, making the fundus less expandable (so it fills up faster) and further helping patients feel full on smaller portions.
The mechanism here is similar to what happens in a surgical sleeve gastrectomy (VSG), where the fundus is removed entirely. In both cases, ghrelin levels drop and the stomach’s capacity is reduced, leading to decreased appetite and earlier satiety. Importantly, GFMA achieves this without removing any organs – it simply remodels the existing stomach lining. The procedure typically takes under an hour and is done as an outpatient therapy. Patients are under anesthesia for comfort, and most go home the same day. So far, the safety profile is excellent: aside from mild nausea or cramping for a day or two, there have been no serious adverse events reported with GFMA in clinical trials. (Patients do take a course of antacid medication for a few weeks after to ensure proper healing and prevent ulcers as the stomach lining regenerates.)
ABLATE I Trial – First Human Results of GFMA
The initial human study of GFMA (a pilot trial) was presented in 2024 and involved 10 adults with obesity. This trial tested GFMA by itself (along with nutritional counseling) to see how well the procedure could reduce hunger and weight. The results at 6 months post-procedure were very encouraging:
- Meaningful Weight Loss: Patients lost ~8% of their total body weight on average (about 9 kg or 20 lbs in six months). Even this moderate weight loss can yield improvements in blood pressure, cholesterol, and diabetes risk, according to experts. It’s important to note that these were early results; longer follow-up is needed, but 8% in 6 months from an endoscopic therapy alone was a strong proof-of-concept.
- Hunger Hormone Plummeted: Fasting ghrelin levels dropped by ~48% after GFMA – from roughly 460 pg/mL before the procedure to about 250 pg/mL at six months. In other words, patients had about half the circulating hunger hormone they started with. This aligns with tissue analyses showing the ablation wiped out approximately 54% of ghrelin-producing cells in the fundus. Such a hormonal change is remarkable because normally when we lose weight, the body raises ghrelin to make us hungrier; GFMA appears to counteract that effect by physically reducing ghrelin sources.
- Smaller Stomach Capacity: The functional size of the stomach fundus shrank significantly. A standard liquid fullness test showed 42% less stomach volume could be tolerated post-procedure (capacity dropped from ~807 mL to 467 mL). Patients got full faster, likely due to the fundus being stiffer and less able to stretch after healing (the scarring acts like an internal gastric “tightening”).
- Less Hunger and “Food Noise”: Patients reported a marked decrease in hunger levels and cravings after GFMA. Using validated surveys, feelings of excessive appetite and urge to eat were reduced by over one-third. Many people with obesity describe constant “food noise” – persistent thoughts about food and difficulty controlling intake. In this trial, GFMA helped quiet that food noise: patients felt noticeably less preoccupied with hunger and more in control of their eating habits. In fact, their self-reported confidence in resisting overeating improved significantly after the procedure.
- Safe and Well-Tolerated: Critically, GFMA was safe. There were zero complications or serious adverse events in the pilot trial. A few participants experienced mild abdominal discomfort or nausea right after the endoscopy, but these side effects were transient and manageable. Overall, the procedure was tolerated very well, especially compared to the recovery profile of any surgical intervention.
These outcomes provided proof-of-concept that endoscopically ablating the stomach’s fundus can indeed lead to weight loss and hunger reduction in humans. It was the first time doctors were able to significantly lower ghrelin via an endoscopic technique in people. While an average 8% total weight loss at 6 months is less than what is typically seen at that point with bariatric surgery or certain medications, it’s a meaningful change given the minimal invasiveness. As Dr. Christopher McGowan (the study’s lead) noted, “The reduction in gastric capacity and hunger is very attractive for patients” – it gives them a sense of control that fad diets alone often can’t. This pilot set the stage for combining GFMA with other therapies to enhance the results even further.
ABLATE II – Combining GFMA with ESG for Maximum Impact
With the success of the first trial, researchers moved to augment GFMA’s effects by pairing it with an endoscopic sleeve gastroplasty. ESG is another incision-free endoscopic procedure in which the stomach is sutured from the inside to make it smaller (much like a surgical sleeve, but without cutting the stomach out). ESG alone can reduce the stomach volume by ~75% and typically leads to about a 15–20% total body weight loss over the first year . The idea in the ABLATE Weight I and II studies was to perform ESG + GFMA together in one session, creating a powerful one-two punch: the ESG physically restricts intake, while the GFMA curbs hunger hormonally. Researchers hoped this combo could approach the effectiveness of a surgical sleeve gastrectomy.
The results did not disappoint. According to data presented in 2025 from the ABLATE I & II trials, the ESG+GFMA combination achieved an average total body weight loss of about 23–24% – essentially surgical-level weight loss without surgery. For context, a typical surgical sleeve gastrectomy often yields roughly 20–25% total body weight loss at one year on average . In these first-in-human combination trials, patients who underwent the dual ESG+GFMA procedure reached ~23% weight loss (similar to what a sleeve gastrectomy can accomplish) and did so with an excellent safety profile. This is a landmark finding – it suggests a minimally invasive endoscopic approach can produce weight loss in the same ballpark as a permanent surgical operation.
Other key outcomes from the combination therapy included:
- Dramatic Hunger Suppression: Patients reported far less hunger and appetite after the combined procedure, in line with the significant ghrelin reductions observed. In both ABLATE I and II groups, ghrelin hormone levels dropped and stayed lower, indicating sustained appetite suppression. This helped patients stick to dietary recommendations more easily, since they simply didn’t feel as hungry as before.
- Smaller Meals, Greater Fullness: The dual effect of a smaller stomach from ESG and a less stretchy fundus from GFMA meant patients felt full with much smaller portions. Their meal capacity was substantially reduced, and satiety (fullness) signals kicked in sooner than pre-procedure. Essentially, ESG+GFMA created a sleeve-like stomach both structurally and functionally, which reinforced healthy portion control.
- Patient Satisfaction and Safety: Combining the two procedures did not compromise safety – there were no serious complications noted in these initial trials (consistent with the standalone GFMA safety). Patients tolerated the procedure well and were typically discharged the same day. Many expressed high satisfaction as they experienced weight loss comparable to surgery without the usual surgical recovery or scars. The term “ESG-MAX” has been coined for this approach, reflecting the maximized weight loss it delivers by adding fundus ablation to the standard ESG .
These findings are groundbreaking. An independent bariatric endoscopy expert (not involved in the study) commented that a dual treatment like this could potentially get patients up to “surgical levels of weight loss without the longer recovery time” of surgery. For patients, that means the possibility of significant, life-changing weight loss with far less downtime, risk, and cost than an operation. Another benefit is that ESG+GFMA is modular – since it doesn’t permanently remove anatomy, it can be combined with other therapies or repeated if needed. It truly opens a new middle path in weight management, fitting between lifestyle/medication approaches and the more drastic surgical route.
How Does GFMA Compare to Surgical Sleeve Gastrectomy (VSG)?
Vertical sleeve gastrectomy (VSG) is a well-known bariatric surgery where about 80% of the stomach (mostly the outer fundus/body) is permanently removed. One reason VSG works so well is that it eliminates the ghrelin-producing fundus, causing patients to have a much lower appetite . The stomach is also much smaller, so it restricts food intake. On average, patients lose 20–25% of their total body weight within ~1 year after a VSG , and hunger is dramatically reduced in that time. Many patients even report having to remind themselves to eat, because their appetite signals diminish so sharply .
GFMA with ESG aims to mimic these effects without actual surgery. In lieu of cutting out the fundus, GFMA “inactivates” it by burning the mucosal layer (which holds the ghrelin cells). ESG, meanwhile, mimics the restrictive aspect by suturing the stomach smaller (though no stomach portion is removed, the inside volume is reduced). The ABLATE trials have shown that combining these can indeed rival the weight loss seen in VSG. Total body weight loss of ~23–24% with ESG+GFMA is comparable to surgical results, and ghrelin levels post-procedure are significantly suppressed (about 45% lower than baseline) – similar in direction to the hormone changes after VSG.
Of course, there are some differences to keep in mind:
- Invasiveness: ESG+GFMA is done through the mouth endoscopically, so no incisions, no stomach stapling, and no removal of organs. VSG is a laparoscopic surgery with incisions and irreversible removal of most of the stomach. This makes ESG+GFMA potentially reversible/adaptable (the stomach lining does grow back to an extent), whereas VSG is permanent. Recovery from ESG+GFMA is faster (days versus weeks) and carries fewer immediate risks.
- Hormone Impact: VSG often causes a larger initial drop in ghrelin since the majority of ghrelin-producing cells are literally cut away. GFMA achieves a substantial reduction (~50%) in ghrelin cells and levels, but perhaps not as complete as surgery. We saw hunger significantly improve with GFMA, though some patients might still have some ghrelin activity remaining. That said, the combination with ESG may compensate by also inducing other satiety hormones from the gut when food intake is reduced.
- Long-Term Durability: Surgical sleeves have long-term data showing maintenance of a significant portion of weight loss for many years (though some regain can occur). For GFMA, being new, we have to observe how durable the effect is. Will the fundus mucosa regenerate over time and ghrelin creep back up? Early signs are positive – ghrelin stayed low through 6+ months, and the scarring of the fundus could create a lasting reduction in its stretchiness. Ongoing studies will track patients at 12, 24 months and beyond. If needed, GFMA could possibly be repeated or touched up endoscopically, something not possible with a removed stomach.
- Degree of Weight Loss: While the average ~23% TBWL with ESG+GFMA is on par with many VSG outcomes, extremely high-weight-loss cases (say 30%+ TBWL) are more routinely achieved with surgery. It remains to be seen if the endoscopic approach can match the upper end of surgical results for the heaviest patients. Nonetheless, reaching the 20%+ TBWL milestone without surgery is a huge advancement and could be sufficient for a large number of patients to achieve health goals.
In summary, GFMA (especially paired with ESG) is emerging as a non-surgical alternative to the surgical sleeve. It imitates the sleeve’s mechanism – reducing stomach size and hunger – from the inside, with the trade-off of being less invasive but needing further research on long-term effects. For patients who desire significant weight loss but are hesitant about surgery, this could be a game-changer.
A Promising Tool in the Fight Against Obesity
The development of gastric fundus mucosal ablation represents an exciting new chapter in bariatric care. It addresses a major aspect of obesity that other non-surgical treatments do not: true appetite reduction at the hormonal level. Until now, there was no medication or minor procedure that could specifically lower ghrelin for the long term – the only option was to physically remove or bypass part of the stomach. GFMA changes that narrative by offering a way to biologically reduce hunger without removing organs. For patients, this means the age-old physiological drive to eat might finally be tamed, making it much easier to stick to healthier portion sizes and diets without feeling miserable. In the ABLATE trials, participants frequently commented on how their relationship with food changed post-procedure – with far fewer cravings and “food noise,” they felt in control rather than controlled by their appetite. This psychological freedom is as important as the numbers on the scale; it’s the difference between white-knuckling through a diet and naturally eating less because your body genuinely isn’t begging for more.
From a safety standpoint, GFMA combined with ESG has shown exceptional tolerability. The fact that hundreds of these ablations have now been done (some outside of trials, as an investigational therapy) with zero serious complications reported is very encouraging. Patients do not have the pain or lengthy recovery associated with traditional bariatric surgery. Most can return to normal activities within a couple of days, and there are no visible scars. Additionally, by avoiding surgery we also avoid the potential nutritional deficiencies or malabsorption issues that can come with procedures like gastric bypass. GFMA’s effects are local to the stomach’s hormone signaling and capacity, which means the rest of the digestive system remains intact and functional.
Clinical significance: The GFMA + ESG approach could fill a critical gap in obesity treatment. We now have medical therapies (like GLP-1 agonist drugs) that can yield significant weight loss, and we have surgery at the high end of the spectrum. Endoscopic therapies like ESG and GFMA offer a middle ground – more effective than medications alone, but less invasive than surgery. Not every patient responds well to medications or can afford to stay on them long-term, and not everyone is eligible for or comfortable with surgery. GFMA provides another option in the toolkit, one that can be delivered in a single session with lasting effects. “We need as many treatment options as possible to address the burden of obesity,” Dr. McGowan noted, emphasizing that some patients prefer a one-time procedure over lifelong meds. The ABLATE trials suggest that GFMA could indeed be that one-time intervention that changes the game for certain individuals.
It’s also worth noting that researchers are already looking at expanded uses for GFMA. Two new trials are underway to see how fundus ablation might help special patient groups: one trial (MAINTAIN) is investigating if GFMA can prevent weight regain in patients who stop taking GLP-1 weight loss drugs, by locking in appetite suppression as they come off the medication. Another trial (REVAMP) is studying GFMA in people who regained weight after a sleeve gastrectomy, to see if ablating any remaining or regenerated stomach mucosa can restart weight loss without a second surgery . These innovative applications highlight GFMA’s potential role not just in primary weight loss, but also in weight maintenance and bariatric revision scenarios. In the coming years, we will learn just how versatile and effective this tool can be across the obesity care continuum.
Bottom line: Gastric fundus mucosal ablation, especially when combined with endoscopic sleeve gastroplasty, is an exciting breakthrough in non-surgical weight management. It attacks obesity on two fronts – reducing how much you can eat and dialing down the drive to eat – all through a scope in a single outpatient visit. Early trials (ABLATE I and II) have demonstrated impressive weight loss (~23% of body weight) on par with surgical outcomes, along with significant reductions in hunger hormones and appetite. And it achieves this with a strong safety profile and minimal downtime for the patient. While longer-term data are still needed, the prospect of a scar-free “sleeve-like” procedure is generating much hope. For bariatric patients seeking effective and durable weight loss without the scalpel – or for those who’ve had surgery and are looking for a boost – GFMA could offer a new lease on life. It exemplifies the ongoing innovation in endobariatric therapy, showing that we can transform patients’ lives by literally ablating hunger at its source. The fight against obesity is far from easy, but with treatments like ESG+GFMA, it’s evolving in a direction that empowers patients with more options, less invasiveness, and newfound optimism for a healthier future.
Sources: The above content is based on findings from Digestive Disease Week presentations and peer-reviewed studies of GFMA, including first-in-human results published in Gastroenterology (Dec 2024) and summary data from the ABLATE Weight I and II trials (presented at DDW 2025). Key results and quotes were drawn from: McGowan CE et al., Gastroenterology 167(7):1457-59, 2024; DDW News coverage; ScienceNews; True You Weight Loss research updates; and other expert commentary . These references substantiate the safety, efficacy, and potential of GFMA with ESG as a transformative, non-surgical approach to weight loss.