#13: Jon and James - GLP-1s: From Lizard spit to liver fibrosis

We're back for Season 2, and Jon and James kick things off with one of their favourite topics: Incretin mimetics. The gut is the biggest endocrine organ in the body, and the data in steatotic liver disease is now as good as anything we have in Hepatology for steatotic liver disease.James and Jon cover the basic pharmacology, how to start and titrate these drugs in practice, what to tell patients about stopping them, the muscle loss question, endoscopy and anaesthesia, and a brief look at where the evidence is going across cardiovascular disease, kidney disease, sleep apnoea, IBD, and cancer. There is a lot going on with these drugs and this episode is the primer.As always comments, questions, feedback and suggestions please send to: X: @2guystalkingit Email: [email protected]:00 Intro: Season 2 is here 03:00 What are incretins? The gut as endocrine organ 06:30 Origin story: Gila Monster and the GLP-1 breakthrough 08:30 The drugs: semaglutide, tirzepatide, and what's coming 10:00 How they actually work: satiety, the brain, and fat oxidation 12:00 Who to start: patient selection and caution groups 13:30 Lean MASH and Southeast Asian BMI thresholds 16:00 Exercise, muscle loss, and the resistance training argument 18:30 Side effects: nausea, constipation, lipase, mood 21:00 Endoscopy and anaesthesia: what to do 24:00 Titrating in practice: James's approach 28:00 Stopping the drug: weight regain and the SURMOUNT data 33:00 Personalising treatment: who can stop, who shouldn't 35:00 Eating disorders, body image, and screening 37:00 MASH data: ESSENCE and Synergy-NASH trials 39:30 Oral formulations: what's available and caveats 40:30 Where bariatric surgery still fits 42:00 Broader indications: IBD, CVD, CKD, cancer 45:00 Global obesity trends and the public health message 47:00 Wrap-upPapers discussedESSENCE trialSynergy-NASH trialSURMOUNT-MAINTAINTirzepatide and fat oxidation, Cell Metabolism 2025GLP-1 receptor agonists and 13 obesity-associated cancersSELECT trialFLOW trialSURMOUNT-OSASTEP 9: Semaglutide in obesity and knee osteoarthritisPsoriatic Arthritis paper