In this episode of the Gladden Longevity Podcast, Dr. Jeffrey Gladden sits down in person with fitness and nutrition expert Autumn Calabrese to unpack the full truth about GLP-1 agonists. With millions of people jumping on semaglutide, tirzepatide, and soon retatrutide, the conversation most doctors aren't having is about what's actually happening inside the body while the scale goes down. Dr. Gladden breaks down how GLP-1s suppress hunger, slow metabolism, and trigger muscle wasting when used without proper diagnostics or a supporting protocol. He explains the critical differences between GLP-1s, GLP-2s, and GLP-3s, reveals why the ghrelin rebound causes most people to regain everything they lost, and shares the strategies he uses in his practice to help patients lose fat while protecting lean tissue. From the 5-day fasting mimicking diet to natural GLP-1 boosters like metabolic probiotics and calocurb, this episode lays out a smarter, more sustainable path to optimizing body composition. Whether you're considering a GLP-1, already on one, or looking for alternatives, this is the conversation that could change your entire approach. For Audience • Use code 'Podcast10' to get 10% OFF on any of our supplements at https://gladdenlongevityshop.com/! • Subscribe to the Gladden Longevity Newsletter for the latest on longevity medicine, peptide protocols, and hormone optimization → https://start.gladdenlongevity.com/subscribe • Ready to find out what's really going on inside your body? Book a call with the Gladden Longevity team → https://start.gladdenlongevity.com/apply-now Takeaways • Peptides are signaling partners, not substitutes for the work your body needs to do. • GLP-1s were designed for diabetics and metabolic syndrome, not casual weight loss. • GLP-1s decrease energy expenditure while GLP-3s (retatrutide) increase it. • Many GLP-1 users are losing muscle mass instead of fat without realizing it. • The ghrelin rebound after stopping a GLP-1 drives appetite higher than before while metabolism stays slower. • A fasting blood sugar and hemoglobin A1C alone are not enough to understand your metabolic health. • A two-hour glucose tolerance test with an insulin curve reveals insulin resistance most doctors completely miss. • The 5-day fasting mimicking diet resets ghrelin, taste buds, gut biome, and leptin sensitivity without destroying muscle. • You can boost your body's own natural GLP-1 production through the right probiotics and bitter receptor activation. • Weight gain is not always an appetite problem. Thyroid dysfunction, declining sex hormones, and missing micronutrients can all be the real driver. • Sex hormone optimization during perimenopause and andropause is critical for maintaining body composition. • Willpower never wins long term. Systems and environment design are what create durable results. Chapters 00:00 Introduction and Welcome with Autumn 00:44 What Is a Peptide and How Peptides Work in the Body 03:07 BPC-157 and the Pharma Model vs. Peptide Signaling 05:00 You Can't Out-Peptide Bad Habits 06:31 What Is a GLP-1 and How It Affects Your Brain and Gut 08:57 GLP-1s Were Designed for Diabetics Not Weight Loss 09:40 GLP-2 Tirzepatide and GLP-3 Retatrutide Explained 11:00 Why Retatrutide Increases Energy Expenditure While GLP-1s Decrease It 12:00 The Muscle Mass Crisis on GLP-1s 14:06 The Patient Who Lost 20 Pounds of Pure Muscle 15:00 Protecting Muscle with Perfect Aminos and Creatine 17:00 Autumn's Personal Supplement Stack for Training 19:00 Food Noise Ghrelin and the Appetite Rebound 21:18 The 5-Day Fasting Mimicking Diet as a Metabolic Reset 23:00 Building Your Own Natural GLP-1 Production 25:00 The Glucose Tolerance Test Most Doctors Never Run 28:30 Risks of GLP-1s Pancreatitis Thyroid Tumors and Unsupervised Use 29:50 Microdosing GLP-1s in Perimenopause 30:30 Calocurb the Natural Appetite Suppressant from Hops 32:00 Sex Hormone Optimization for Body Composition 35:00 Resting Metabolic Rate Testing and Hidden Thyroid Dysfunction 38:00 Autumn's Hormone Health Program and Real Results 39:30 Willpower vs Systems and Architecting Your Environment 41:30 Bio-Individuality and Why Someone Else's Plan Won't Work for You 43:00 The Power of Diagnostics and Understanding Your Genetics To learn more about Autumn: Instagram: @autumncalabrese Reach out to us at: Facebook: https://www.facebook.com/Gladdenlongevity/ Instagram: https://www.instagram.com/gladdenlongevity/?hl=en LinkedIn: https://www.linkedin.com/company/gladdenlongevity YouTube: https://www.youtube.com/channel/UC5_q8nexY4K5ilgFnKm7naw Gladden Longevity Podcast Disclosures Production & Independence The Gladden Longevity Podcast and Age Hackers are produced by Gladden Longevity Podcast, which operates independently from Dr. Jeffrey Gladden's clinical practice and research at Gladden Longevity in Irving, Texas. Dr. Gladden may serve as a founder, advisor, or investor in select health, wellness, or longevity-related ventures. These may occasionally be referenced in podcast discussions when relevant to educational topics. Any such mentions are for informational purposes only and do not constitute endorsements. Medical Disclaimer The Gladden Longevity Podcast is intended for educational and informational purposes only. It does not constitute the practice of medicine, nursing, or other professional healthcare services — including the giving of medical advice — and no doctor–patient relationship is formed through this podcast or its associated content. The information shared on this podcast, including opinions, research discussions, and referenced materials, is not intended to replace or serve as a substitute for professional medical advice, diagnosis, or treatment. Listeners should not disregard or delay seeking medical advice for any condition they may have. Always seek the guidance of a qualified healthcare professional regarding any questions or concerns about your health, medical conditions, or treatment options. Use of information from this podcast and any linked materials is at the listener's own risk. Podcast Guest Disclosures Guests on the Gladden Longevity Podcast may hold financial interests, advisory roles, or ownership stakes in companies, products, or services discussed during their appearance. The views expressed by guests are their own and do not necessarily reflect the opinions or positions of Gladden Longevity, Dr. Jeffrey Gladden, or the production team. Sponsorships & Affiliate Disclosures To support the creation of high-quality educational content, the Gladden Longevity Podcast may include paid sponsorships or affiliate partnerships. Any such partnerships will be clearly identified during episodes or noted in the accompanying show notes. 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