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On The Pen With Dave Knapp

On The Pen With Dave Knapp

De: Bleav Dave Knapp Founder of On The Pen
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Dave Knapp brings you your weekly dose of everything in the news about incretin mimetic, diabetes and obesity therapies, like Zepbound and Mounjaro, Ozempic and Wegovy, and even investigational treatments like CagriSema and Retatrutide!© 2025 On The Pen With Dave Knapp Enfermedades Físicas Higiene y Vida Saludable Política y Gobierno
Episodios
  • Retatrutide Weight Loss: How Much At Each Dose

    Retatrutide Weight Loss: How Much At Each Dose
    Dec 13 2025

    https://www.otplinks.com

    0:00 Welcome & today’s focus: Retatrutide and “chasing the biggest number”
    1:11 On The Pen intro, live schedule (Mon/Wed/Fri) & housekeeping
    2:10 How Dave first heard about retatrutide (work trip, early phase 1 data)
    3:35 Flashback clip: early excitement about retatrutide phase 3 trials
    4:40 Why this new retatrutide data feels different for obesity medicine
    5:32 TRIUMPH-4 trial overview: obesity + knee osteoarthritis population
    7:00 Headline results: 28.7% average weight loss, surgery-level efficacy
    8:47 Breaking down weight loss by dose (9 mg vs 12 mg; 25–35% loss rates)
    11:05 What “efficacy estimate” really means (race-track analogy)
    13:28 Real-world view: treatment-regimen estimate (20–23.7%) vs trial ideal
    15:40 Mechanism refresher: GIP, GLP-1, glucagon and why RETA differs from TIRZ
    18:05 Side effects, dysesthesia/allodynia & who stopped treatment (BMI differences)
    21:02 Why the lower doses matter & who actually needs 30% weight loss
    24:15 From “just make the scale go down” to quality of weight loss & body composition
    28:05 Future focus: health, longevity, and peptides beyond hitting goal weight
    30:40 Viewer Q&A: combining RETA + TIRZ, amylin (eloralintide) combos & “talk to your doctor”
    34:38 How retatrutide changes the next decade of obesity treatment conversations
    37:22 News update: high-dose Wegovy 7.2 mg approval in the EU & US outlook
    40:55 Orforglipron oral GLP-1: liver-signal concerns & fast-track FDA review
    45:20 Why small-molecule oral GLP-1s aren’t the same as injectable peptides
    48:40 New topic: Indiana “Safe Drug Act of 2025” and why Dave is concerned
    51:02 Production caps, “essentially a copy” language & shifting power from prescribers to FDA
    54:28 How the bill undermines personalization while ignoring real safety tools
    57:05 Safety theater vs real safeguards: API sourcing, sterility & adverse-event reporting
    59:45 Who actually gets hit: compliant 503A/503B compounders vs existing bad actors
    1:02:05 Call to action: petition at otplinks.com & why patient voices matter
    1:05:10 Change.org impact, media attention & centering the patient perspective
    1:07:30 Final Q&A, subscribe, obesity.news email list & closing thanks


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    50 m
  • Mounjaro vs. New Obesity Drugs: Why Wave-007 Is Stealing the Spotlight

    Mounjaro vs. New Obesity Drugs: Why Wave-007 Is Stealing the Spotlight
    Dec 9 2025

    Episode Timeline & Main Topics

    00:00 — Opening & Community Update
    • First week doing the podcast fully live thanks to the On The Pen community
    • Overview of why this week’s news is a major turning point in obesity medicine

    02:30 — Introducing the “One-and-Done” Obesity Drug (Wave Life Sciences)
    • WVE-007 early data drops
    • Why this therapy is unlike GLP-1s or any nutrient-stimulated hormone
    • Fat loss results and lean-mass increase

    06:30 — How Wave-007 Works: INHBE Gene Silencing
    • Mechanism behind visceral fat reduction
    • Why this shifts the field toward “quality of weight loss”

    09:15 — Why Lean-Mass Preservation Matters
    • Current GLP-1 medications and muscle loss
    • Why women dominate trial enrollment and the larger implications
    • Medicare patients and the coming wave of GLP-1 coverage

    13:45 — The Future of Maintenance Therapies
    • Fractyl Health Revita results
    • Lilly’s orforglipron maintenance design
    • Why “holding the line” after GLP-1 therapy is the next major category

    17:30 — Amylin Agonists: Cagrelintide vs. Eloralintide
    • Novo’s delays and the strategy behind them
    • Lilly’s surprising phase 2 results (up to 20% weight loss)
    • Combination therapies with tirzepatide or retatrutide

    22:30 — FDA Pipeline Acceleration
    • Potential removal of traditional phase 3 trials
    • How this speeds up the arrival of next-generation therapies

    24:15 — Oral GLP-1 Small Molecules (Structure Therapeutics)
    • Alaniglipron data and the stock surge
    • Comparisons to orforglipron and past failures like denuglipron
    • Why Dave remains skeptical

    28:40 — Sponsor Break: Shed & Shapa
    • Access, coaching, and patient support
    • Using a numberless scale to build a healthier relationship with weight tracking

    31:10 — Counterfeit Ozempic Warning
    • New fake lot discovered in U.S. pharmacies
    • How to identify counterfeit pens
    • Why this should be a national headline
    • The broader question of drug supply-chain vulnerability

    36:00 — Closing Thoughts on the Future of Obesity Medicine
    • Moving from “more weight loss” to “better weight loss”
    • Why the field is closer than ever to reshaping obesity as a disease
    • Gratitude for the community making full-time coverage possible


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

    GLP-1: New Metrics, New Molecules, New Prices
    Dec 2 2025
    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 ...
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    30 m
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This is my go to info on how to handle dr’s, updated meds info, compounding, and how to talk about obesity as a disease. Love it!

Great for all the latest updates

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Dave is a super star in the GLP-1 world, He is proficient in dispelling the mis- and disinformation that is rampant in the GLP-1 space, allowing consumers to learn and make informed, educated health care decisions partnered with their health care providers. His information is cutting edge, using trusted sources, and his is the sole reliable voice in patient education in GLP-1 meds and obesity treatment. With the pace of recent and ongoing advances in treating the chronic condition of obesity, his expertise as an industry insider is needed and so appreciated. Thank you, Dave, for advocating for us. I value every one of your episodes, and follow you on all platforms.

Super star patient educator

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