What if Oprah Knew About Fractyl Health?

Oprah Winfrey recently revealed that when she stopped taking her GLP-1 medications, she gained 20 pounds in 12 months. She thought she could maintain the weight loss by diet and exercise alone, and chose to wean herself off the drugs so that she would not be dependent on them. But once she regained the weight, she realized that she couldn’t battle obesity without some help. She is now taking the medications again.

Looks like Winfrey could be the perfect target candidate for Fractyl Health, a medical device company that is running clinical trials for an outpatient procedure to help people who want to get off GLP-1s without regaining all the weight.

“The unmet need is shifting heavily towards solving this post-GLP-1 weight regain problem,” said Harith Rajagopalan, co-founder and CEO of the Burlington, Massachusetts-based medtech company, in a recent interview in San Francisco.

On Thursday, the company announced 6-month data for its ongoing REMAIN-1 Midpoint Cohort trial that showed that people who underwent the Revita procedure had slower weight regain than those in the sham control group. In fact, Revita-treated patients had a 4.5% weight regain compared with 7.5% in the sham arm at 6 months.

The blinded, sham-controlled study evaluated 45 people for safety and efficacy, with five people being excluded from the efficacy group per study protocol because they did not comply with lifestyle and diet requirements.

REMAIN-1 also found that people who had higher-than-the-median weight loss due to GLP-1 drug intake also gained the weight at a much lower rate. At 6 months, these patients saw a 4.2% weight regain versus 13.3% in the sham group.

So, what is the Revita procedure?

Revita is an outpatient endoscopic procedure where a flexible scope passes into the digestive tract targeting the duodenum. Then, hydrothermal ablation remodels the duodenal lining to resurface the mucosal layer. The entire procedure takes less than 40 minutes.

Rajagopalan believes that a lifetime of high-fat and high-sugar diets leads to a dysfunction in the duodenum and thereby difficulty maintaining a healthy weight and blood glucose control. Revita’s ablative procedure is intended to reverse that.

And some data from the trial may be proof of some measure of improving metabolic health post-GLP-1 discontinuation in patients treated with ablation. At 6 months, patients who underwent the Revita procedure saw increased HDL or good cholesterol compared with those in the sham control group — 15.5 vs 3.9 mg/dL — and reduced triglyceride-to-HDL ratio — -0.2 vs +0.4.

More efficacy data is expected later this year, but Fractyl, buoyed by what it views as compelling clinical data, is going to be seeking a new regulatory pathway for the device from the FDA — the De Novo pathway for low-to-moderate risk profiles — as opposed to the more burdensome, though more rigorous, PMA premarket approval.

Despite the positive data, the markets have not reacted too kindly. The company, which went public in 2024, saw its stock tumble in pre-market trading. It closed at 58 cents down 68%. Not that the market is rational all the time but could Wall Street investors have been expecting even lower or zero weight regain after GLP-1 discontinuation and Revita treatment compared to the sham control group?

In its announcement, the company noted, “The Midpoint Cohort was not designed to be sufficiently powered for efficacy analysis.” Rajagopalan and his team will have six more months to prove that the procedure is safe and effective.

But it has already had to adjust to market realities.

When the company went public in February 2024, Rajagopalan cast the company’s product as providing long-term, lasting weight loss, something not achievable with GLP-1 drugs. The company was focused on reversing Type 2 diabetes and had even launched a study, which was paused last January. And now, given how revolutionary GLP-1s have been in causing rapid weight loss — CMS began covering them for obesity last year — and the challenge of maintaining that weight loss after stopping the injections, the company has had to pivot to targeting patients who are keen to keep their weight down without the medication.

But the universe of these patients, including those like Winfrey who have tried unsuccessfully, is large, Rajagopalan said, in our meeting during the annual J.P. Morgan Healthcare conference.

“I think patients are anxious about the idea of taking this chemical for the rest of their lives and being dependent on this chemical in order to be able to keep their weight lower. You see that on Twitter, Reddit, social media message boards all the time. There is this fundamental anxiety that ‘I’m addicted to this medicine in order to keep my weight down,'” he said. “‘If I ever stop it for whatever reason, I’m going to rebound very aggressively’, that causes them concern.”

And then there are side effects of the drug, which force people to get off them as well. And those side effects are compounded in oral GLP-1s, he said. These oral medications are expected to widely improve access and adoption of GLP-1s.

“Anything that increases access for patients to therapies at work, we’re all for. But it actually also really helps us because the more people who start on orals, the more people are going to stop taking any GLP-1s, oral or injectable,” he said. “Phase three [data] shows that the side effects on pound per pound weight loss are greater with the orals than they are with the injectables.”

Before the REMAIN Midpoint study, Fractyl Labs reported 6-month results from an open-label study that showed that people who stopped taking tirzepatide after losing an average of 50 pounds and undergoing the company’s treatment effectively maintained that body weight loss for six months.

“The trajectory of their weight looks so much better than what you’ve seen from Lilly or Novo’s studies of GLP-1 discontinuation,” he said.

While that may be true, time is running out for Fractyl Health, which was originally founded in 2010 under the name MedCatalyst.

“Narrative pivots are hard. It takes time for people to come around to them,” Rajagopalan said, noting that 2026 will be a crucial year for the company.

Photo: Peter Dazeley, Getty Images