Dr Robert Kushner on GLP-1s, appetite biology and coming off the drug

Save 20% on all Nuzest Products WORLDWIDE with the code MIKKIPEDIA at www.nuzest.co.nz, www.nuzest.com.au or www.nuzest.comCurranz Supplement: Use code MIKKIPEDIA to get 20% off your first order - go to www.curranz.co.nz  or www.curranz.co.uk to order yours NZ listeners - save 10% off Calocurb by using the code Mikkipedia10 at www.calocurb.co.nzEpisode SummaryThis week Mikki talks with Dr Robert Kushner, an obesity medicine physician, educator and researcher with over four decades in the field. He is Professor Emeritus at Northwestern University Feinberg School of Medicine, a founder and the first chair of the American Board of Obesity Medicine, and a past president of The Obesity Society. He was also the corresponding author on the STEP 1 semaglutide trial published in the New England Journal of Medicine in 2021, and sat on the steering committee for SELECT — so he has watched this field from the inside, before and after GLP-1 receptor agonists arrived.The conversation traces what clinicians actually understood about obesity in the 1980s and 90s, Bob's own leptin trial and why it did not deliver, and how reframing obesity as a biological disease led researchers to the gut hormones. From there it moves into the practical territory: how the clinical conversation has shifted from counting calories to diet quality, which side effects are real and which are social media noise, what happens to muscle mass and physical function, how dose escalation should actually work, why hunger returning is not the same as weight regain, and what the evidence says about stopping. Bob is careful throughout to separate what the trials show from what is still unknown, which makes this a useful listen whether you work with clients on these medications or are weighing them up yourself.Key TopicsWhat clinicians believed about obesity three decades ago — excess body fat was known to cause system-wide harm, but the mechanisms, and appetite dysregulation in particular, were not understood, and weight regain after lifestyle intervention was already expectedBob's own leptin trial in the 1990s, published in JAMA, and why leptin turned out to be a useful biological signal rather than a treatment — it defends against weight loss but was never built to stop overeatingThe STEP 1 result and why it changed the field: 15% average weight loss at 68 weeks against a previous benchmark of 6–9%, with a third of participants losing 20%How the clinical conversation shifted from quantity to quality — when the medication does the heavy lifting, the questions become whether someone is eating enough, staying hydrated and getting sufficient protein, rather than how to control cravingsWhich side effects are real and which are overstated: GI effects are the genuine shared profile and can be substantially reduced through diet during dose escalation, while hair thinning and facial fat loss follow large weight loss by any routeMuscle mass, sarcopenia and the groups who need watching, alongside the consistent finding that physical function and quality of life improve in trials — possibly because fatty infiltration of muscle resolvesDose escalation in the real world versus the trial protocol, and why there are still no pretreatment predictors of who will respondWhy appetite drifting back is normal and not a failure — Bob's framing of restored appetite regulation at a lower body weight, with "the amplitude smaller than it was before"Benefits beyond weight loss, including SELECT's 20% reduction in cardiovascular events on top of standard care, plus sleep apnoea, knee osteoarthritis, MASH and psoriasis — driven both by weight loss and by independent mechanismsCost and access, microdosing, extending the interval between injections, and where bariatric surgery still fitsChapters00:00 Introduction05:13 Obesity medicine before GLP-1s13:34 Gut hormones and the STEP 1 result21:00 From calorie counting to diet quality25:00 Side effects and social media myths29:54 Muscle mass, function and exercise35:08 Dose escalation and who responds40:30 When hunger comes back46:37 Stopping the drug, cost and access52:24 Benefits beyond weight loss57:37 Long-term safety and microdosing1:01:10 Coming off, surgery and what's nextGuest / ResourcesDr Robert KushnerProfessor Emeritus, Nor