Retatrutide: Investigating the Number of Users and Its Impact on Muscle Mass, Plus an FDA Update and Food Analysis App

On The Pen™ GLP-1 News

Introduction to Retatrutide and User Numbers [0:00]

The host, Dave Napman, initiates a discussion around the triple agonist, Retatrutide, also known as the "GLP3" (though this term is clarified as inaccurate, as only GLP1 and GLP2 exist in the body). He questions whether over a million people have already tried this next-generation metabolic modulating drug, which he also refers to as an "anti-obesity medication" and a "longevity drug."

• Clinical Trial vs. Real-World Usage [0:50]:
  • Official clinical trials for Retatrutide have involved approximately 7,500 people, with some receiving a placebo.
  • Despite this, Napman believes that millions have tried research-grade Retatrutide, citing social media trends and online forums.
• Social Media Influence [5:25]:
  • Prior to TikTok's crackdown on Retatrutide content, videos promoting its use garnered up to 50,000 likes.
  • Even with censorship, discussions using code words for "Ratatouille" (a common misspelling/code word for Retatrutide) continue to proliferate, indicating widespread interest.
  • A Reddit forum dedicated to Retatrutide receives over 160,000 unique weekly visitors, sometimes exceeding 200,000.
  • Prominent influencers, like Dr. Trevor Bachmeier with millions of views on Retatrutide content across platforms, often link to research-grade peptide companies, suggesting a clear path to purchasing the substance.
• Unprecedented Usage [11:14]:
  • Napman highlights the unprecedented scale of an investigational medication being used by millions before regulatory approval and market launch.
  • He emphasizes that this widespread use is not limited to those with advanced metabolic disease, but also includes individuals seeking general health improvements or muscle-sparing benefits.

Retatrutide's Role and Comparison to Tirzepatide [2:00]

Napman clarifies that Retatrutide is not a direct successor to Tirzepatide, even though both are from Eli Lilly.

• Target Patient Population [2:11]:
  • Eli Lilly intends Retatrutide for patients with more advanced metabolic disease.
  • The majority of patients are expected to remain on dual agonists like Zepbound, Tirzepatide, or Mounjaro.
• Mechanism of Action & Novelty [2:47]:
  • Stimulating three receptors does not automatically mean it's better for everyone.
  • Retatrutide introduces the novel concept of long-acting glucagon receptor agonism.
  • There is currently no long-term data on the effects of stimulating glucagon receptors over time, especially in non-diabetic populations.
  • Long-acting glucagon is a new and novel peptide, and it comes with potential trade-offs, being a cardiac-stimulating peptide.
• Factors Influencing Choice [3:31]:
  • Individual patient needs, goals, and doctor's willingness to prescribe will dictate usage.
  • Cost and insurance coverage are significant limiting factors.
• Market Prediction [3:52]:
  • Napman disputes Andrew Huberman's prediction that Retatrutide will be the first trillion-dollar drug, arguing that Tirzepatide is likely to be larger due to its broader patient population.

Understanding Muscle Mass Loss with Weight Loss Medications [12:14]

A significant portion of the discussion addresses the misconception that Retatrutide is uniquely muscle-sparing.

• Misconception [13:00]:
  • Many online users, particularly in bodybuilding and fitness communities, claim Retatrutide is muscle-sparing, unlike other GLP-1s. This is contradicted by available data.
• Mechanism of Action (Revisited) [13:17]:
  • While previous anti-obesity medications work centrally (reducing appetite), Retatrutide's glucagon component acts peripherally, allowing for increased calorie expenditure.
  • Increased physical activity, especially resistance training, could indirectly help preserve muscle mass, but it's not an inherent property of the molecule itself.
• Clinical Data on Lean Mass Loss [13:59]:
  • Phase 2 clinical trials, specifically a body composition substudy published in The Lancet, showed that Retatrutide-induced weight loss was approximately 75% fat mass and 25% lean mass.
  • This proportion of lean mass loss is comparable to other weight loss methods:
    • Bariatric surgery: ~21% fat-free mass loss.
    • Diet & Exercise: 20-30% lean mass loss.
    • Non-GLP1 pharmacotherapy (e.g., phentermine, bupropion/naltrexone): 25-30%.
    • GLP1 pharmacotherapy:
      • Tirzepatide: 25%
      • Semaglutide: up to 39% (noted as "uniquely problematic")
      • Liraglutide: up to 15%
  • Retatrutide's 25% lean mass loss is "on par, not better than" current therapies, disproving the muscle-sparing claim.

    

  • Implications for Patients [18:50]:
    • With medications achieving 30% weight loss, comparable to bariatric surgery, monitoring body composition and muscle mass preservation becomes crucial.
    • Techniques like DEXA scans and body composition scales are important tools.
    • Especially for the elderly population, maintaining muscle mass is critical for long-term health outcomes.

FDA Clampdown on Compounded GLP-1 Medications [39:38]

The discussion shifts to regulatory actions affecting access to GLP-1 medications.

• Eli Lilly vs. Mochi Health Lawsuit [39:51]:
  • A court hearing was held regarding Eli Lilly's lawsuit against Mochi Health, a telehealth provider, concerning compounded GLP-1s.
  • Unlike a similar case by Novo Nordisk that was dismissed, the judge in the Eli Lilly case appeared more favorable to Eli Lilly, suggesting the lawsuit will proceed.
• FDA Commissioner's Warning [40:46]:
  • Dr. Marty Makary, an FDA Commissioner, tweeted about the FDA's continued observation of "unapproved GLP1s being mass marketed."
  • He stated these drugs can be "risky and ineffective" and that the FDA "will continue to go after companies that are violating our regulations."
  • The tweet included an image of compounded semaglutide pills, which Napman identifies as an advertisement from Mochi Health, directly linking FDA action to the ongoing lawsuit.
• Impact on Patients [42:20]:
  • The impending "clampdown" necessitates that individuals relying on compounded medications from telehealth providers explore other options with their doctors to avoid treatment interruptions.
  • Hundreds of thousands of people using research-grade Retatrutide could lose access.
• Previous FDA Actions [42:40]:
  • Earlier in the week, the FDA seized Retatrutide at the border, further indicating a tightening of regulations.
• Medicare Coverage and Muscle Preservation [53:05]:
  • Medicare will start covering GLP-1 medications for qualifying individuals in July, and more broadly in January of next year under certain plans.
  • This expanded access makes the conversation about muscle mass preservation even more critical, especially for the elderly, who are more susceptible to negative outcomes from lean mass loss during rapid weight loss.

Navigating Food Choices with the Terra App [23:39]

Hambone, the co-host, introduces a new app designed to help consumers make informed food choices.

• Terra App Overview [23:41]:
  • The Terra app (icon: green mushroom, T E R R A) allows users to scan barcodes of food products.
  • It goes beyond basic nutrition labels (calories, macros, fiber, sodium).
  • It assesses "Metabolic Impact" based on five criteria:
    1. Seed Oils
    2. Additives
    3. Added Sugars/Sweeteners
    4. Processing Level
    5. Toxins
• Examples and Scores [25:30]:
  • Graham Crackers: Scored 0 out of 100 due to presence of seed oils, additives, added sugars, high processing, and toxins.
  • Coffee Creamers: Many received 0 scores, even those with "health claims," except for Chobani (score of 21), which still contained sugars, sweeteners, and additives. Hambone notes personal issues with gums as additives.
  • Bubbl'r Antioxidant Sparkling Water: Surprisingly scored 0 due to additives, sugars, and high processing, despite its "antioxidant" branding.
  • Synergy Guava Goddess Kombucha: Received an "excellent" 100% rating for minimal processing, absence of toxins, additives, and seed oils. However, it contains 16 grams of sugar (3 added grams), highlighting that app scores should be considered alongside individual dietary needs (e.g., for diabetics).
  • Granola Baked Bar: Scored 0.
  • Think Protein Bar: Scored 0 due to seed oils, additives, added sugar, medium-high processing, and high to medium-high toxins.
• App Benefits and Limitations [31:28]:
  • The app offers a comprehensive view of food quality, combining nutritional and environmental aspects.
  • It helps users avoid guesswork regarding processed ingredients.
  • Users should still consider their personal biology, specific needs, and allergies, as a high score doesn't negate potential issues like high sugar content for diabetics.
  • The app is particularly useful for identifying highly processed foods that are often disguised as healthy options (e.g., hospital cafeteria snacks).