On The Pen With Dave Knapp

• GLP-1: New Metrics, New Molecules, New Prices

  Topics We Cover: 00:00 – New data from Harvard/Mass General may classify nearly 70% of adults as having obesity 03:00 – A new oral triple agonist shows record-setting absorption rates 07:00 – Fractal Health’s Revita procedure: weight maintenance after stopping GLP-1s 12:00 – Zepbound vial prices drop (full breakdown by dose) 16:00 – Dave’s personal experience switching off Mounjaro and intense hunger return 22:00 – Novo Nordisk’s EVOKE/EVOKE+ Alzheimer’s trial: what the data really means 29:00 – Why GLP-1 neurological research is just getting started 33:00 – Updates on access, partners, and major news coming soon for Medicare patients If you’re on Wegovy, Mounjaro, Zepbound, Saxenda, Trulicity, or compounded versions, this episode gives you the insight and context you need to have more competent and confident conversations with your doctor. Bullet Point Summary of the Podcast Episode New Obesity Measurement Data (Harvard/Mass General Study) Harvard and Mass General propose adding waist circumference to BMI to better diagnose obesity. Traditional BMI misses key factors like muscle mass and body composition. Using the updated measure, Americans classified as obese jumps from ~43% to almost 69%. This means 7 out of 10 U.S. adults would now qualify as having the disease of obesity. Dave notes this validates many people who “feel” metabolically unwell despite a “normal” BMI. Reinforces his claim that “most people should be talking to their doctors about GLP-1s.” New Oral Triple Agonist (Ascletis – ASC41/ASC? Molecule) From Ascletis (A-S-C-L-E-T-I-S), developing an oral triple agonist targeting: GLP-1 GIP Glucagon Similar in mechanism to retatrutide, expected around 2027. Preclinical (animal) data show stunning results: Oral bioavailability of 4.2% 9× higher than tirzepatide 30× higher than oral semaglutide 6× higher than oral retatrutide 57× greater drug exposure than oral retatrutide Half-life ~56 hours Stronger receptor activation than retatrutide in vitro Suggests potential for the first powerful oral triple agonist—worth watching. ️ 3. Discussion of the Gray Market / TikTok Experience Dave briefly recounts losing his TikTok account and landing in an algorithm filled with teenagers promoting gray-market “retatrutide.” Expresses concern over unregulated peptide sales, especially to minors. Fractal Health’s New Data – Weight Maintenance After Stopping GLP-1s New results from the Reveal One study (Fractal Health). Participants: lost 24% of body weight on GLP-1s → stopped injections → got one Revita procedure. At 6 months post-GLP-1 discontinuation: Weight changed only 1.5% (vs. ~10% regain in typical off-drug trials) HbA1c barely shifted Safety profile clean Suggests possible long-term weight maintenance without injections through gut mucosal re-lining. Dave describes his own recent attempt to switch drugs and significant hunger return. Food Noise & Biologic Hunger Dave discusses how stopping Mounjaro caused terrifying, primal hunger. Describes the distinction between: Food noise (brain-based thoughts) Hunger signals (biological/animalistic) Reinforces why many patients cannot maintain weight loss without support. Zepbound (Tirzepatide) Cash-Pay Price Reductions Eli Lilly drops cash-pay vial pricing: 2.5 mg: $349 → $299 5 mg: $499 → $399 7.5–15 mg: $499 → $449 Community feedback (informal poll): Most say still too high to leave compounded versions. Many would switch to branded if price hit $200–$300. Dave notes the Most Favored Nations agreement will push GLP-1 prices toward $250/month within 24 months. Alzheimer’s Study (Novo Nordisk – EVOKE & EVOKE+) Oral semaglutide (Rybelsus, 14 mg) did not slow Alzheimer's clinical progression. Biomarkers improved but daily function and cognitive decline did not improve vs placebo. Important context: Oral Rybelsus is a weak form of semaglutide; stronger versions (like Wegovy 2.4 mg or upcoming high-dose oral Wegovy) not tested. Weight loss is not desirable in Alzheimer’s patients, influencing drug selection. Dave emphasizes: This was a nearly $700M trial and an act of scientific courage. This is NOT the end of GLP-1 Alzheimer’s research. Future molecules may target neurological pathways without suppressing appetite. Mentions Lilly’s brenipatide, a GIP receptor agonist being developed for: Addiction Opioid dependency Possibly asthma ️ 8. Access, Cost, and Patient Empowerment Highlights Shed as a partner offering telehealth GLP-1 access. Notes many patients hide GLP-1 use from their primary care doctors. Reinforces OTP’s mission: better, more honest conversations with clinicians. Shapa (Numberless Scale) & Dave’s Personal Update Dave explains how the Shapa numberless scale helped him stay engaged during weight fluctuations. Finds stepping on “zones” (green/gray/blue) less emotionally damaging than numbers. Closing Notes Promises upcoming Eli Lilly savings card update. Encourages subscribing, liking, and enabling notifications for algorithm visibility. Thanks OTP community for amplifying patient-centric obesity medicine news. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

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• Novo Nordisk Amycretin Shocker + Semaglutide Flopper

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• Wegovy GLP-1 Price Novo Blinks First

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• GLP-1 State of the Union

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• Lower Cost Zepbound and Wegovy? TrumpRX Announcement Incoming

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