Oprah Winfrey not too long ago revealed that when she stopped taking her GLP-1 medicines, she gained 20 kilos in 12 months. She thought she may preserve the burden loss with weight loss program and train alone, and selected to taper off the medicines so she would not be depending on them. However as soon as she regained her weight, she realized she could not struggle weight problems with out some assist. She is now taking the treatment once more.

It looks as if Winfrey may very well be the proper candidate for Fractyl Well being, a medical system firm that’s conducting scientific trials for an outpatient process to assist individuals who wish to eliminate GLP-1 with out gaining all the burden again.

“The unmet want is shifting sharply towards fixing this post-GLP-1 weight achieve drawback,” mentioned Harith Rajagopalan, co-founder and CEO of the Burlington, Massachusetts-based medtech firm, in a current interview in San Francisco.

On Thursday, the corporate introduced six months of knowledge for its ongoing REMAIN-1 Midpoint Cohort research, which confirmed that individuals who underwent the Revita process had slower weight achieve than these within the sham management group. In actual fact, Revita-treated sufferers had a 4.5% weight achieve in comparison with 7.5% within the sham arm at 6 months.

The blinded, sham-controlled research assessed 45 individuals for security and efficacy, with 5 individuals excluded from the efficacy group per research protocol as a result of they didn’t meet way of life and dietary necessities.

REMAIN-1 additionally discovered that individuals who had higher-than-average weight reduction on account of taking GLP-1 medicine additionally gained weight at a a lot slower price. After 6 months, these sufferers noticed a weight achieve of 4.2%, in comparison with 13.3% within the sham group.

So, what’s the Revita process?

Revita is an outpatient endoscopic process by which a versatile scope is inserted into the digestive tract, concentrating on the duodenum. Then, hydrothermal ablation remodels the duodenal lining, resurfacing the mucosal layer. Your entire process takes lower than 40 minutes.

Rajagopalan believes {that a} lifetime of weight-reduction plan excessive in fats and sugar results in duodenal dysfunction and due to this fact issues in sustaining a wholesome weight and blood glucose management. Revita’s ablative process is meant to reverse that.

And a few knowledge from the research could present proof of a point of enchancment in metabolic well being after discontinuation of GLP-1 in sufferers handled with ablation. After 6 months, sufferers who underwent the Revita process noticed elevated HDL or good ldl cholesterol in comparison with these within the sham management group – 15.5 vs. 3.9 mg/dL – and a decreased triglyceride-to-HDL ratio – -0.2 vs. +0.4.

Extra efficacy knowledge are anticipated later this 12 months, however Fractyl, backed by what it considers compelling scientific knowledge, will search a brand new regulatory pathway for the system from the FDA – the De Novo pathway for low to average threat profiles – versus the extra onerous, however rigorous, pre-market PMA approval.

Regardless of the constructive figures, the markets haven’t reacted too kindly. The corporate, which went public in 2024, noticed its shares plummet in pre-market buying and selling. It closed at 58 cents, down 68%. Not that the market is at all times rational, however may Wall Road buyers have anticipated even decrease or zero weight achieve after discontinuation of GLP-1 and Revita therapy in comparison with the sham management group?

Within the announcement, the corporate famous: “The Midpoint Cohort was not designed to be adequately powered for efficacy evaluation.” Rajagopalan and his workforce could have one other six months to show that the process is protected and efficient.

However it has already needed to adapt to market realities.

When the corporate went public in February 2024, Rajagopalan pitched the corporate’s product as one that may ship long-term weight reduction, one thing not achievable with GLP-1 medicine. The corporate was targeted on lowering sort 2 diabetes and had even began a research, which was halted final January. And now, given how revolutionary GLP-1s have been in inflicting fast weight reduction — CMS began overlaying them for weight problems final 12 months — and the problem of sustaining that weight reduction after stopping the injections, the corporate has needed to deal with sufferers who wish to preserve their weight with out the treatment.

However the universe of those sufferers, together with these like Winfrey who’ve tried with out success, is huge, Rajagopalan mentioned once we met on the annual JP Morgan Healthcare convention.

“I feel sufferers are involved concerning the concept of ​​taking this chemical for the remainder of their lives and being depending on this chemical to maintain their weight down. You see that on a regular basis on Twitter, Reddit and social media message boards. There’s a elementary concern that ‘I am hooked on this drug to maintain my weight down,'” he mentioned. “If I ever cease for any purpose, I’ll bounce again very aggressively,” which worries them.”

After which there are the negative effects of the drug, which pressure individuals to return off it as effectively. And people negative effects are exacerbated with oral GLP-1s, he mentioned. These oral medicines are anticipated to broadly enhance entry and adoption of GLP-1s.

“Something that will increase affected person entry to office therapies, we’re all for that. However it additionally actually helps us as a result of the extra individuals begin taking oral medicines, the extra individuals will cease taking GLP-1s, oral or injectable,” he mentioned. “Section three [data] reveals that the negative effects on weight reduction per pound are better with the orals than with the injectables.”

Earlier than the REMAIN Midpoint research, Fractyl Labs reported six-month outcomes from an open-label research displaying that individuals who stopped taking tirzepatide after shedding a mean of fifty kilos and taking the corporate’s therapy successfully maintained that weight reduction for six months.

“Their weight trajectory appears to be like so significantly better than what you’ve got seen from the Lilly or Novo research on discontinuing GLP-1,” he mentioned.

Whereas that could be true, time is working out for Fractyl Well being, which was initially based in 2010 as MedCatalyst.

“Narrative pivots are troublesome. It takes time for individuals to adapt to them,” Rajagopalan mentioned, noting that 2026 can be a pivotal 12 months for the corporate.

Photograph: Peter Dazeley, Getty Pictures