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/…

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.

Holy crap.

@ManOnThePen Often just reflexive pushback

@harithr The unhinged pushback against this is wild to me.

With a clear focus on reducing rates of obesity and metabolic disease, the single biggest driver of morbidity and mortality in the modern era, this new pyramid is totally sensible

@JCanNuSH @ManOnThePen My cofounder @jdcaplan always says that the diseases are only "chronic" because the treatments suck. If we had curative treatments, the diseases wouldn't be called chronic.

@harithr @ManOnThePen But if a procedure becomes available so that my chronic condition is no longer chronic, I’ll be very happy for that. Looking forward to the next Revita readout! $GUTS

I’ve been saying it for a while, even had disagreements with obesity docs on this. There is something special about the GLP-1 hormone that is cardiac protective, something that the GIP molecule doesn’t possess. Pre-clinical data may explain why. (biorxiv.org/content/10.110…) Clinical data points to it, including Lilly’s own dula V tirz study. This post marketing data shows it IRL… We love tirzepatide for many reasons, but when it comes to matters of the heart, there’s something special about GLP-1. $LLY $NVO $VKTX

@JCanNuSH @ManOnThePen Totally unreasonable to expect people to stay on any med for the rest of their lives unless doing so has immediate symptomatic benefit (eg, acute pain control; addictive meds).

@ManOnThePen Also look at how they had no deaths in the on protocol group. Speaks to how few managed to stay on protocol.

Totally agree. Treating obesity is not monolithic; each of GLP-1, GIP, amylin, etc., will have slightly different metabolic effects and will depend on patient subtype. Effects individually will not be the same as effects combinatorially (something most Mendelian geneticists fail to grasp). We will only know what really matters from large scale real world studies, as Phase 3 programs are skewed and artificial due to clinical development gamesmanship.

Hi @statnews and @cooney_liz! As you know, we will have randomized data later this month on #Revita for post-GLP-1 weight maintenance and pivotal data later this year on this exact topic. Post-GLP metabolic rebound is the biggest problem in obesity, and we need better solutions. Revita has FDA breakthrough designation but is not approved by FDA. We anticipate PMA filing this year.

As we close out 2025, I am struck by how far we have come and how much opportunity lies ahead. This year, we advanced our clinical programs, deepened our science, and strengthened the foundation for what could become a fundamentally new chapter in obesity and type 2 diabetes treatment. 2026 will be a defining year. We expect multiple clinical readouts across Revita® and the start of first-in-human studies for our Rejuva® gene therapy platform. Each step brings us closer to durable, root-cause-driven treatments that could reshape long-term metabolic health. I am profoundly grateful for the dedication and belief of everyone on our team. Your work is making it possible to imagine a future where patients have options that truly change their trajectory. Wishing everyone a healthy and inspiring start to the new year. Big things are ahead. *Revita® is for Investigational Use Only in the U.S. under Federal law* *Rejuva® is in preclinical development and has yet to be assessed by regulatory agencies.*