New Data on Retatrutide is out and it Needs to Be Talked About

The phase three trial data for retatrutide just dropped at the American Diabetes Association conference and the numbers are unlike anything we have seen from an obesity drug before. 30% average weight loss. One in four patients lost more than 35% of their body weight. Bariatric surgery outcomes from a weekly injection. Dr. Spencer and Dr. Karl sit down with guest David W, a nurse practitioner who was actually enrolled in the Triumph 1 phase three trial for retatrutide. He started at 240 pounds with a BMI of 34, lost down to 167, and is now sitting at 175 on tirzepatide maintenance. He breaks down what it felt like to be on the drug, what the side effects were really like during dose escalation, and what happened when the trial ended and he switched back to tirzepatide. They also get into how retatrutide is different mechanistically from tirzepatide, why glucagon agonism matters for liver fat and lipid metabolism, the gray market research peptide problem, the biologic classification fight with the FDA, how Spencer is thinking about switching patients from tirzepatide to retatrutide once it is approved, the dizziness and hypotension signal in hypertensive patients, and what the upcoming Triumph 3 cardiovascular outcomes trial could mean for how broadly this drug gets used. What you'll learn: What retatrutide is and how it differs from tirzepatide as a triple agonist What David W experienced as a phase three trial participant from side effects to weight loss Triumph 1 obesity trial results including average weight loss and categorical outcomes at 80 and 104 weeks How sleep apnea and knee arthritis outcomes compare to tirzepatide and semaglutide Transcend type two diabetes trial results and what near normal A1C looks like after 40 weeks Why the LDL reduction signal is significant and what mechanisms are driving it Who should actually be a candidate for retatrutide versus staying on tirzepatide How Spencer plans to switch patients from tirzepatide to retatrutide in practice Why the gray market research peptide version carries real risk What the FDA biologic classification debate means for compounding and access This podcast is for education and entertainment purposes only. The physicians on this podcast are not your physician. This is not personalized medical advice. Always consult your healthcare provider regarding your specific health concerns. 0:00 – Intro, Guest David W, Nurse Practitioner and Triumph 1 Trial Participant 1:03 – What Is Retatrutide, Triple Agonism Explained, GLP-1 GIP and Glucagon 4:25 – How Retatrutide Relates to Tirzepatide, Same GIP Backbone With Three Amino Acid Changes 7:16 – David's Trial Experience, Dose Escalation Side Effects, Heartburn and Loose Stools 9:48 – 240 Pounds to 167 Pounds, What Switched to Tirzepatide Felt Like After the Trial 11:34 – Triumph 1 Trial Overview, Basket Trial Design, Obesity Plus Sleep Apnea Plus Knee Arthritis 13:11 – Baseline Characteristics, 2400 Patients, Average BMI 40, 36% Pre-Diabetic 15:16 – Bottom Line Weight Loss Results, 19% at Four Milligrams, 26% at Nine, 28% at Twelve Milligrams 17:23 – Categorical Weight Loss, Three Out of Four Patients Hit 20%, One in Four Hit 35% Plus 18:41 – Bariatric Surgery Level Outcomes, Extension Trial Results at 104 Weeks 19:04 – Side Effect Profile, GI Rates by Dose, UTI Signal and Dizziness in Hypertensive Patients 22:37 – Discontinuation Rates, Placebo Dropouts From Ineffective Weight Loss, Excessive Weight Loss Cases 24:02 – Sleep Apnea 60% Reduction, Knee WOMAC Score 70% Reduction, Comparison to Tirzepatide 24:49 – Blood Pressure Drop, Lipid Panel Results, 41% Triglyceride Reduction, 20% LDL Reduction 26:01 – Why the LDL Reduction Is Different, Glucagon Effects on Liver Lipid Metabolism 27:10 – Transcend Type Two Diabetes Trial, 40 Weeks, No Other Diabetes Medications Allowed 29:59 – Diabetes Trial Results, A1C Down to 5.9 to 6.2, Near Normal Average Blood Sugars 32:37 – Weight Loss in Diabetic Patients, Comparison to Tirzepatide Surpass One Trial 34:17 – Who Should Get Retatrutide, Gray Market Research Peptide Warning, Clinical Use Plan 37:44 – How to Switch Patients From Tirzepatide to Retatrutide in Practice 39:34 – FDA Biologic Classification Fight, Compounding and Access Implications 41:00 – Triumph Three Cardiovascular Outcomes Trial, Triumph Eight Low Dose Trial, What Is Coming