Harith Rajagopalan

Today, we announced an important milestone for Fractyl Health and the future of obesity care. For the first time, randomized, blinded clinical data from the REMAIN-1 Midpoint Cohort demonstrate that Revita® may prevent weight regain after GLP-1 discontinuation at 3 months. In the study, patients treated with Revita continued to lose weight following GLP-1 withdrawal, while sham patients regained weight (–2.5% vs. +10%, p=0.014). These findings suggest that drug-free, durable weight maintenance may be possible. We believe Revita has the potential to serve as a one-time intervention that could transform the standard of care—much like LASIK did for vision. The implications are significant: shifting from a focus on temporary weight loss to sustaining health through a durable metabolic reset. With pivotal studies ahead, Revita may help define a new therapeutic category in obesity: post-GLP-1 weight maintenance. This is just the beginning of the journey. #FractylForward $GUTS #obesity #weightmaintenance Revita® is for Investigational Use Only in the U.S. under Federal law. ir.fractyl.com/news-releases/…

While nearly 18% of U.S. adults have taken a GLP-1 drug for weight loss or to treat a chronic condition, about half of people will stop taking it within a year. Often, they don’t understand what is likely to come next. 🔗: on.wsj.com/4dCkbia

Duodenal mucosal resurfacing procedure may offer a way for the estimated 70% of people who discontinue weight-loss drugs to avoid regaining weight, the findings indicate that this minimally invasive procedure may provide lasting weight-loss maintenance tinyurl.com/3zdtawud

@houmanhemmati The body would produce more endogenous GLP-1 hormone

💉 🧬 The European drug regulators are allowing a Phase 1 clinical trial of a GLP-1 gene therapy. Imagine a one-shot Wegovy or Zepbound, where your body produces the drug. Lots of questions & possibilities. What if you have a bad reaction or don’t need it anymore? Turn off? What do you think?

Highly recommend this presentation from Dr Ania Jastreboff, lead researcher for many obesity trials, including SURMOUNT-1, which lead to Zepbound’s FDA approval, and the upcoming TRIUMPH-1 trial on retatrutide. She argues that obesity stems from an inappropriate setting of the defended fat mass by the metabolic system which causes the brain to inappropriately signal for more food consumption because it has incorrectly determined that the individual needs to increase their fat mass. These meds re-regulate that, resetting the defended fat mass to lower levels, reducing the brains signals to eat more, and allowing individuals to lose weight. The upcoming retatrutide will not just change appetite/craving signaling, but will also increase energy expenditure itself.

What happens after stopping GLP-1s? That’s the question Revita is designed to answer. New interview with @Medtech_Insight on durability, the duodenum, and the road to pivotal data in early Q4. Revita is investigational use only in the US. Full interview here: insights.citeline.com/medtech-insigh…

DDW 2026: Revita highlighted as a potential post-GLP-1 ‘off-ramp’ strategy in DDW News, featuring our REMAIN-1 interim midpoint results. Oral presentation scheduled for Monday, May 4. Full pivotal data targeted later 2026. Revita is investigational use only in the US. @FractylHealth @FractylHealth news.ddw.org/news/duodenal-…

Proud to see coverage of our REMAIN-1 interim midpoint data in @Reuters: In the study, Revita DMR-treated patients (highest-dose group) maintained >80% of weight loss with ~7 lb regain at 6 months after stopping GLP-1s like tirzepatide, vs. ~ double in sham. Revita is Investigational Use Only in the US. Full pivotal cohort data and potential regulatory submission planned later 2026. reuters.com/business/healt…

Huge news on FDA - CMS partnership on Breakthrough Devices - RAPID program designed to dramatically accelerate access fda.gov/news-events/pr…

Largest life science M&A of the week - Penumbra acquired by BSC for $15B after FY revenue of $1.4B. This large deal should help recycle capital for high growth device stories; and may have gone unnoticed by many tx investors… 🤔 where should one look for potentially high growth opportunities? $GUTS

The headline speaks for itself - for all those who think discontinuation is an “access” issue versus a “health” definition, please note Oprah tried to stop her GLP-1 $GUTS dailymail.co.uk/health/article…

@Alice_MiaX That is so disheartening. Why did they stop taking it?

I have two women in my neighborhood who went on Ozempic. They lost a ton of weight and felt amazing. One felt so amazing she got a divorce…true story. I saw them both this past week… and the weight’s back. So yeah, turns out Ozempic doesn’t come with a lifetime warranty.

@ManOnThePen For sure!

@harithr Would love to have you back to OTP to discuss when it comes out!

Remain-1 midpoint data anticipated later in January $GUTS futurism.com/health-medicin…

Roughly 85% of people who start a GLP-1 stop it within 2 years. Weight and cardiovascular benefit are lost when they do. Raises an obvious question: are phase 3 drug studies in obesity asking the most important and relevant question, or are they a scientific exercise with diminishing real world relevance? Shouldn’t the market care more about what works in the real world when it evaluates new products? medscape.com/viewarticle/we…

You seem to be a surgeon. Let me remind you that that there are only three types of food: fat, protein, carbs. Any sentient human would know that processed carbs are bad for you. You’re not left with too many other choices: fat and protein. Don’t like the “cattleman?” What’s left?

The new pyramid is performance dressed up to look like science. Increasing saturated fat and letting the cattleman industry get a seat at the table isn't making America Healthy Again - it is strengthening the one ingredient that increases the number one killer in America. If you wanted a true, scientific look at better diets, we have two with years of data and real world experience - the DASH and Mediterrnanean. But instead throw another bone to the food industry, these ones have cowboy hats instead of ties and their proponents often go shirtless eating rib eyes and denying that saturated fat increases heart disease. My cardiologists will be busier if anyone pays attention to this upside down pyramid.

@TheTech1vestor @Ajayatmithril @ManOnThePen @Pharmdca @Anders_Research @hormonedietdoc @TeslaBoomerMama @NSradar @semodough @BioStocks @Bio_youtuber . The time is ripe for a weight maintenance solution. We've been saying for years that value in the obesity market will eventually accrue to maintenance rather than loss because that is what ultimately matters

☝️ $GUTS @harithr @Ajayatmithril @ManOnThePen @Pharmdca @Anders_Research @hormonedietdoc @TeslaBoomerMama @NSradar @semodough @BioStocks @Bio_youtuber

$GUTS Former GLP-1 users regain lost weight after about 18 months, study says washingtonpost.com/wellness/2026/…

@celinegounder The weight regain is biological, not behavioral. The weight setpoint is messed up in obesity, only masked temporarily by GLP-1s.

GLP-1s and the Weight Rebound Problem After Stopping Weight-Loss Drugs, Pounds and Health Risks Return Quickly, Studies Find Read & subscribe here: open.substack.com/pub/drcelinego…

@celinegounder Hi @celinegounder!

@CoachDanGo 💯

It’s crazy to see people coming out with arguments against eating real food. I’m convinced that if some people hear the right information from someone they don’t like they’ll take it in bad faith regardless.