Passionate about breaking the pattern of metabolic disease. Co-Founder and CEO, @FractylHealth @BrighamWomens Med/CVMed | @JohnsHopkins MD PhD | @Stanford Chem
Boston
Joined March 2010
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Harith Rajagopalan retweeted
The gut is much more than a digestive organ. It is a metabolic sensing and signaling system that helps shape how we respond to food, regulate appetite, and control metabolism.
Really enjoyed going deep on this with Andrew Huberman, from gut biology and the microbiome to obesity, GLP-1 therapies, and endoscopic treatments.
The new Huberman Lab episode is out: Best Tools for Gut Health and Weight Loss | Dr. Chris Thompson
0:00 Dr. Chris Thompson
2:16 Digestive Tract, Gut Hormones & Nutrient Absorption
8:06 Colon Microbiome & Colon Cancer Screening
11:13 Sponsors: LMNT & Lingo
13:40 Swallowing Problems & Zenker's Diverticula
16:08 Bowel Movements & Constipation
18:28 Fiber, Resistant Starch & the Gut Barrier
21:50 Intermittent Fasting & the Gut Microbiome
23:38 Fermented Foods, Microbial Diversity & Butyrate
27:12 H. pylori, Stress & Stomach Ulcers
30:20 GLP-1 Medications: Benefits & Limitations
33:42 Lower GLP-1 Doses, Weight Regain & Muscle Loss
37:35 GLP-1 Side Effects, Food Noise & Apathy
39:49 Bariatric Surgery & Medical Innovation
46:07 Sponsor: AG1
47:44 Hunger & Satiety: Ghrelin, CCK, GIP & GLP-1
50:01 Retatrutide & Combining Hormonal Targets
52:55 Ultra-Processed Foods, Overeating & Leptin
55:32 Incretin Discovery, Exendin-4 & the Gila Monster
59:35 Endoscopic Ultrasound & Pancreatic Biopsy
1:07:40 Early Metabolic Markers, CGMs & Fasting Insulin
1:13:06 Insulin Resistance & Metabolic Flexibility
1:15:53 Sponsor: Function
1:17:35 Patient Data, Screening & Treatment Adoption
1:26:31 AI, Robotics & Improving Procedures
1:29:27 Choosing a Surgeon & Measuring Procedure Quality
1:35:29 Image Guidance & Hyperspectral Imaging
1:37:19 Sponsor: Our Place
1:38:56 Diagnostics & Targeted Metabolic Treatments
1:42:45 Gastric Bypass, Foregut Exclusion & Diabetes
1:47:59 Duodenal Liners & Mucosal Resurfacing Research
1:52:58 Gut Permeability, Inflammation & Fatty Liver
1:59:39 Artificial Sweeteners, Fructose, Fats & Omega-3s
2:05:00 Resistance Training, Zone 2 Cardio & Intervals
2:06:31 Weight Set Point & Metabolic Adaptation
2:08:13 Endoscopic Sleeve Gastroplasty & Fundus Ablation
2:10:30 Magnetic Intestinal Connections & Combined Treatments
2:16:52 GLP-1 Gene Therapy Research
2:22:13 Innovation, Problem Solving & Teamwork
2:25:58 Zero-Cost Support, Sponsors & Neural Network Newsletter
Includes paid partnerships.
Harith Rajagopalan retweeted
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
Harith Rajagopalan retweeted
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
Harith Rajagopalan retweeted
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.
Harith Rajagopalan retweeted
Dr. Kristina Lewis of @WakeForest shares the stark contrast between what's happening in clinical trials and clinical practice with respect to continuous use of #obesity #medication
👉 Why are rates lower in clinical practice? Access, cost, coverage, side effects, effectiveness...
👉 Are the lower rates problematic or ideal?
Join the conversation today at nhlbi.nih.gov/events/2025/ni… @NIH
Harith Rajagopalan retweeted
$GUTS $LLY $NVO $HIMS
🚨 MASSIVE NEW GLP-1 DATA:
Patients who stopped their #GLP1 after losing 24% of their body weight held those results for 6 months after a SINGLE #Revita procedure.
Only 1.5% weight change. No bounce back. Usual regain after stopping GLP-1s is closer to 10%.
This is shaping up to be a real solve for regain after discontinuation.
#fractylforward #onthepen #offthepen
Harith Rajagopalan retweeted
$lly $nvo $guts
The Revita program from @FractylHealth is extremely promising.
Patient who stopped Tirzepatide and got the procedure kept losing, those who stopped and didn’t get it gained 10% back!
More data coming in 2026!
Harith Rajagopalan retweeted
Honored to join the Board of Fractyl Health at such a pivotal moment. Revita® is advancing through late-stage development, and Rejuva® is preparing for first-in-human studies. Fractyl is redefining how we treat obesity and type 2 diabetes by addressing root causes, not just symptoms. Excited to help shape this next chapter.
Harith Rajagopalan retweeted
Yet another study showing high discontinuation rate of both semaglutide and tirzepatide up to 50% at 1 year in the real world.
Top discontinuation reasons included:
• Side effects (36%)
• Logistical challenges (24%)
• Cost (23%)
• Shortages (11%)
• Inadequate weight loss (7%)
Excellent talk by Dr. Satya Dash at #ENDO2025
Harith Rajagopalan retweeted
Will initial use of GLP-1 medicines serve as a portal for endoscopic and surgical approaches to maintain #weightloss nature.com/articles/d41586-0… @NatureNV @ElieDolgin
Harith Rajagopalan retweeted
model says tirzepatide is cost-effective but only by assuming:
📌 5 years of perfect adherence
📌 Benefits persist long after stopping- not proven
📌 Discounted drug prices (not what payers actually pay)
📌 A 30y time horizon
Real-world? Much less certain
Tirzepatide is cost-effective with a $3092 per QALY in people with #obesity and type 2 #diabetes
dom-pubs.onlinelibrary.wiley…
Harith Rajagopalan retweeted
Modern pharmacotherapy may be efficacious. However, adherence to treatment is low
🚨A new study published in @JAMANetworkOpen revealed how many adults with overweight or #obesity do not continue #GLP1 therapy for more than 1 year, regardless of type 2 #diabetes status.
@ZekeEmanuel @Truveta @PennMEHP @GoHealio
healio.com/news/endocrinolog…
Harith Rajagopalan retweeted
We've got some exciting news... we're rolling out a refreshed brand identity and website! Our rebrand is a pivotal moment, reflecting the transition of Fractyl Health: who we are, where we’re headed, & our commitment to our patients. See our new look at fractyl.com.
Harith Rajagopalan retweeted
During the 17-week trial-off Tirzepatide period, many people experienced weight recurrence and some converted to T2D, reducing the Tirzepatide diabetes prevention effect to 88% (10% lower than after the experimental phase).
💡Takeaway: Chronic disease requires chronic treatment.
🚨 BREAKING: SURMOUNT-1 Extension Top-line Results Are In!
🔥 3-Year Diabetes Prevention Extension Study with Tirzepatide
✅ 22.9% Average Weight Loss
✅ 94% Risk Reduction in Developing Type 2 Diabetes
investor.lilly.com/news-rele…
Harith Rajagopalan retweeted
PHARMA HISTORY: Top 10 BY MARKET CAP
2004: Pfizer “King of Lipids - Lipitor”
2005-11: JNJ “TNF Time - Remicade”
2012: Roche “HER Too - Herceptin”
2013-21: JNJ “Bloody Blockbuster - Imbruvica”
2022-23: Lilly “The Obesity Show - Mounjaro”
Source: Joana Sadowska on the HR APP
Harith Rajagopalan retweeted
The American Diabetes Association (ADA) 84th Scientific Sessions starts today in Orlando, Florida.
We will be presenting new preclinical data for our investigational product REJUVA® on Sunday, June 23rd, from 1:30-1:45 p.m. ET, in the Valencia Ballroom.
This abstract was recognized as noteworthy and selected by the Scientific sessions Meeting Planning Committee as one of eight President’s Select Abstracts. #ADA2024 #ADAScientificSessions #Fractyl #obesity #type2diabetes #T2D #biotechinterview
*Rejuva is in preclinical development and has yet to be assessed by regulatory agencies
Harith Rajagopalan retweeted
GLP-1 medicines started with injectable GLP-1RAs, then moved to oral peptides, and now co-agonists. The future will usher in multiple new ways of delivering GLP-1 medicines, and activating GLP-1R signaling pathways, promising improved efficacy/convenience. diabetesjournals.org/care/ar…
Harith Rajagopalan retweeted
🔹Over 30% of GLP-1 users discontinue medication within the 1st month, according to commercial insurance data.
🔹Over half discontinue before 3 months.
🔹There is a lower discontinuation rate when meds are prescribed by endocrinologists or obesity medicine specialists, and those that were seen for follow-up sooner.
bcbs.com/sites/default/files…
Harith Rajagopalan retweeted
Fractyl Health, Inc. (Nasdaq: GUTS) is excited to share our findings at #DDW2024! Stop by booth #312 and don’t miss Sunday’s plenary presentation titled poster presentation, "Single-Dose GLP-1-Based Pancreatic Gene Therapy: Sustaining Weight Loss Post Semaglutide Discontinuation and Diminishing Hepatic Triglycerides in an Obesity Mouse Model." 103AB, May 19, 4-5:30pm ET. #type2diabetes #health #obesity #genetherapy #biotech
Harith Rajagopalan retweeted
Fractyl Health, Inc. (Nasdaq: GUTS) (the “Company”) today announced 6-month follow-up data from its enrolling German real-world registry study of Revita® for T2D. Check out these real-world findings which further support the potential of Revita for durable maintenance of weight loss. ir.fractyl.com/news-releases… #type2diabetes #health #obesity #biotech
* In the United States, Revita is for investigational use only under US law.