Have you heard about retatrutide?
It's the weight loss drug everybody is talking about. People are buying it online as a research chemical, and patients ask me if I'm prescribing it (I'm not).
A study in the New England Journal of Medicine shared insights into the drug, which is currently not FDA-approved. At the highest dose, people lost an average of 25% of their body weight over 80 weeks, compared with about 4% body weight for those on placebo. The area I care about most—muscle—doesn’t get much attention.
In this episode, I go through the TRIUMPH-1 results, how retatrutide compares with semaglutide and tirzepatide, and what protein and resistance training do for muscle during weight loss.
Find Dr. Gabrielle Lyon at:
- Instagram: https://www.instagram.com/drgabriellelyon/
- TikTok: https://www.tiktok.com/@drgabriellelyon
- Facebook: https://facebook.com/doctorgabriellelyon
- YouTube: https://youtube.com/@DrGabrielleLyon
- X (Twitter): https://x.com/drgabriellelyon
- Apply to become a patient – https://drgabriellelyon.com/new-patient-inquiry/
- Join my weekly newsletter – https://institute-for-muscle-centric-medicine.ck.page
Chapters:
00:00 Cold open: weight loss we have never seen before with a drug
00:45 TRIUMPH-1 and phase three: a trial of retatrutide in people without diabetes
02:49 Approval and mechanism: phase three is not FDA approval, and retatrutide hits GLP-1, GIP and glucagon
04:53 The headline: 25% of body weight, about 62 pounds, against 15% for semaglutide and 21% for tirzepatide
06:52 Trial design: 2,339 adults, 80 weeks and no prescribed diet
08:45 Results by dose: 17 to 28% on retatrutide, about 4% on placebo and the bariatric surgery comparison
10:29 The top dose: more than half dropped below a BMI of 30, plus the 104-week extension
13:10 Beyond the scale: waist, blood pressure, triglycerides, insulin, CRP, knee pain and sleep apnea
15:37 The muscle question: TRIUMPH-1 does not report body composition
16:32 Phase 2 DEXA data: about 30 to 40% of weight lost was lean tissue
18:22 Protein and training: the 1.2 versus 2.4 g/kg deficit study
20:24 The goal: lose fat and keep muscle
21:29 Pharmacology: SURMOUNT-5 put tirzepatide at 20% against 14% for semaglutide
22:30 What glucagon adds, and why there is no head-to-head trial yet
25:23 Side effects, and why more drug is not better medicine
27:23 What TRIUMPH-1 changes, and the study still missing
28:48 Not FDA approved, and where obesity pharmacology goes next
29:51 Close: the goal was never weight loss
Study and References:
Jastreboff AM, Kaplan LM, Davies MJ et al. 2026. Retatrutide, a triple hormone receptor agonist, for treatment of obesity. N Engl J Med. DOI: https://doi.org/10.1056/NEJMoa2604169
Coskun T et al. 2025. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. PMID: 40609566 https://pubmed.ncbi.nlm.nih.gov/40609566/
Longland TM et al. 2016. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. PMID: 26817506 https://pubmed.ncbi.nlm.nih.gov/26817506/
Aronne LJ et al. 2025. Tirzepatide as compared with semaglutide for the treatment of obesity. PMID: 40353578 https://pubmed.ncbi.nlm.nih.gov/40353578/
Wilding JPH et al. 2021. Once-weekly semaglutide in adults with overweight or obesity. PMID: 33567185 https://pubmed.ncbi.nlm.nih.gov/33567185/
Jastreboff AM et al. 2022. Tirzepatide once weekly for the treatment of obesity. PMID: 35658024 https://pubmed.ncbi.nlm.nih.gov/35658024/
Disclaimer: The Dr. Gabrielle Lyon Podcast and YouTube are for general information purposes only and do not constitute the practice of medicine, nursing, or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this podcast, YouTube, or materials linked from this podcast or YouTube is at the user's own risk. The content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they may have and should seek the assistance of their health care professional for any such conditions.
