Dr. Spencer Nadolsky and Karl break down two brand new randomized controlled trials that put hard numbers on a question they have been navigating clinically for years: what actually happens to patients on GLP-1 medicines when they try to lower their dose, switch to a cheaper option, or come off entirely.
In this episode they cover why obesity biology actively fights back against weight loss through hunger hormones, fat cell hormones, and hypothalamic signaling in ways that make maintenance genuinely hard for most people and not a failure of willpower, what the Surmount-4 trial showed about weight regain when people came off tirzepatide after losing an average of 21 percent of their body weight and why that 17 percent who maintained their weight off medication is a number that keeps showing up across multiple studies, what the brand new Surmount-Maintain trial did by reducing some patients from their maximum tolerated dose of tirzepatide down to five milligrams and what that meant for weight outcomes at 112 weeks, why the average line graph in these trials can make it look like everyone on the max dose kept their weight off when the waterfall plots tell a more complicated story with roughly 25 to 30 percent of people on the highest dose still not maintaining 85 percent of their weight loss, what rescue tirzepatide was and why two thirds of placebo patients needed it, what the Attain-Maintain trial tested by switching patients who finished Surmount-5 from tirzepatide or semaglutide over to orforglipron and whether an oral GLP-1 can hold the weight that an injectable one lost, why orforglipron is not yet cost efficient enough for most patients as a maintenance strategy despite the promising data, why Spencer and Karl both see fewer than five percent of their own patients regain significant weight on the maximum tolerated dose and what that gap between clinical experience and trial data might be telling us, the weight independent benefits of GLP-1 medicines including blood sugar control and cardiovascular effects that matter even if weight stays the same, and why people injecting unapproved research peptides like retatrutide without FDA approval or human safety data is something both doctors find genuinely alarming.
The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode. Hosted by Simplecast, an AdsWizz company. See <a href="https://pcm.adswizz.com">pcm.adswizz.com</a> for information about our collection and use of personal data for advertising.

<description>&lt;p&gt;Dr. Spencer Nadolsky and Karl break down two brand new randomized controlled trials that put hard numbers on a question they have been navigating clinically for years: what actually happens to patients on GLP-1 medicines when they try to lower their dose, switch to a cheaper option, or come off entirely.&lt;/p&gt;
&lt;p&gt;In this episode they cover why obesity biology actively fights back against weight loss through hunger hormones, fat cell hormones, and hypothalamic signaling in ways that make maintenance genuinely hard for most people and not a failure of willpower, what the Surmount-4 trial showed about weight regain when people came off tirzepatide after losing an average of 21 percent of their body weight and why that 17 percent who maintained their weight off medication is a number that keeps showing up across multiple studies, what the brand new Surmount-Maintain trial did by reducing some patients from their maximum tolerated dose of tirzepatide down to five milligrams and what that meant for weight outcomes at 112 weeks, why the average line graph in these trials can make it look like everyone on the max dose kept their weight off when the waterfall plots tell a more complicated story with roughly 25 to 30 percent of people on the highest dose still not maintaining 85 percent of their weight loss, what rescue tirzepatide was and why two thirds of placebo patients needed it, what the Attain-Maintain trial tested by switching patients who finished Surmount-5 from tirzepatide or semaglutide over to orforglipron and whether an oral GLP-1 can hold the weight that an injectable one lost, why orforglipron is not yet cost efficient enough for most patients as a maintenance strategy despite the promising data, why Spencer and Karl both see fewer than five percent of their own patients regain significant weight on the maximum tolerated dose and what that gap between clinical experience and trial data might be telling us, the weight independent benefits of GLP-1 medicines including blood sugar control and cardiovascular effects that matter even if weight stays the same, and why people injecting unapproved research peptides like retatrutide without FDA approval or human safety data is something both doctors find genuinely alarming.&lt;/p&gt;
&lt;p&gt;The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode.&lt;/p&gt;&lt;br/&gt; &lt;p&gt;Hosted by Simplecast, an AdsWizz company. See &lt;a href="https://pcm.adswizz.com"&gt;pcm.adswizz.com&lt;/a&gt; for information about our collection and use of personal data for advertising.&lt;/p&gt;</description>

2:26 PMClaude responded: Dr.Dr. Spencer Nadolsky and Karl break down two brand new randomized controlled trials, Surmount-Maintain and Attain-Maintain, that put hard numbers on what actually happens to patients when they try to lower their tirzepatide dose, switch to oral orforglipron, or come off GLP-1 medicines entirely after significant weight loss. The data confirms what they have been seeing clinically for years: obesity biology fights hard to pull weight back up, only about 17 percent of people can come off these medicines and maintain their results, and for most patients the conversation is not about stopping but about finding the most effective and affordable long-term dosing strategy.

GLP-1 Maintenance: What Happens When You Lower Your Dose, Switch Medications, or Stop Entirely

Dr. Spencer Nadolsky and Karl sit down with Dr. Susan Brian, a Yale-trained endocrinologist, certified menopause provider, and medical director of a clinic with seven endocrinologists who runs an active bone fragility fracture clinic, to answer the question that has been flooding social media since a viral abstract with two fake bones on a surgical table convinced people their skeletons are quietly dissolving. <a href="https://www.instagram.com/susanbrianmd/" target="_blank" rel="noopener noreferrer">Follow Dr. Susan here</a>
In this episode they cover why the preclinical and mechanistic data on GLP-1 medicines actually points toward bone benefit rather than harm by improving osteoblast activity and reducing osteoclast activity, why the meta-analyses from over two decades of GLP-1 use in type 2 diabetes show reduced fracture risk rather than increased risk, what the recent Israeli retrospective cohort study actually found and why an 11% increased fragility fracture signal in older adults on GLP-1 for diabetes versus other treatments deserves attention without panic, why almost every nutritional deficiency flagged in GLP-1 patients turns out to be vitamin D deficiency that likely predated the medicine, why the degree of weight loss matters far more than the medicine itself and how the one to two pounds per week threshold and the one percent of body weight per week guideline translate into real clinical practice, what the Hansen JAMA 2024 study showed about GLP-1 alone versus GLP-1 with resistance training and why that finding is the single most important takeaway for anyone on these medicines, why Spencer has idiopathic hypercalciuria and was spilling 650 milligrams of calcium per day in his urine before anyone caught it, how romosozumab works and why it is the most powerful bone building medicine available, why Dr. Brian orders baseline bone densities on patients well before the standard screening age and why insurance almost always covers it, and why comparing GLP-1 nutritional risk to bariatric surgery nutritional risk is not even close to an apples to apples comparison.
The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode. Hosted by Simplecast, an AdsWizz company. See <a href="https://pcm.adswizz.com">pcm.adswizz.com</a> for information about our collection and use of personal data for advertising.

<description>&lt;p&gt;Dr. Spencer Nadolsky and Karl sit down with Dr. Susan Brian, a Yale-trained endocrinologist, certified menopause provider, and medical director of a clinic with seven endocrinologists who runs an active bone fragility fracture clinic, to answer the question that has been flooding social media since a viral abstract with two fake bones on a surgical table convinced people their skeletons are quietly dissolving.&lt;br&gt;&lt;br&gt;&lt;a href="https://www.instagram.com/susanbrianmd/" target="_blank" rel="noopener noreferrer"&gt;Follow Dr. Susan here&lt;/a&gt;&lt;/p&gt;
&lt;p&gt;In this episode they cover why the preclinical and mechanistic data on GLP-1 medicines actually points toward bone benefit rather than harm by improving osteoblast activity and reducing osteoclast activity, why the meta-analyses from over two decades of GLP-1 use in type 2 diabetes show reduced fracture risk rather than increased risk, what the recent Israeli retrospective cohort study actually found and why an 11% increased fragility fracture signal in older adults on GLP-1 for diabetes versus other treatments deserves attention without panic, why almost every nutritional deficiency flagged in GLP-1 patients turns out to be vitamin D deficiency that likely predated the medicine, why the degree of weight loss matters far more than the medicine itself and how the one to two pounds per week threshold and the one percent of body weight per week guideline translate into real clinical practice, what the Hansen JAMA 2024 study showed about GLP-1 alone versus GLP-1 with resistance training and why that finding is the single most important takeaway for anyone on these medicines, why Spencer has idiopathic hypercalciuria and was spilling 650 milligrams of calcium per day in his urine before anyone caught it, how romosozumab works and why it is the most powerful bone building medicine available, why Dr. Brian orders baseline bone densities on patients well before the standard screening age and why insurance almost always covers it, and why comparing GLP-1 nutritional risk to bariatric surgery nutritional risk is not even close to an apples to apples comparison.&lt;/p&gt;
&lt;p&gt;The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode.&lt;/p&gt;&lt;br/&gt; &lt;p&gt;Hosted by Simplecast, an AdsWizz company. See &lt;a href="https://pcm.adswizz.com"&gt;pcm.adswizz.com&lt;/a&gt; for information about our collection and use of personal data for advertising.&lt;/p&gt;</description>

Dr. Spencer Nadolsky and Karl sit down with Dr. Susan Brian, a Yale-trained endocrinologist and certified menopause provider who runs a bone fragility fracture clinic, to break down whether GLP-1 medicines are actually causing bone loss or whether the viral panic around this topic is getting ahead of the evidence. The short answer is that the medicines themselves do not appear to be the problem, the weight loss is, and there is a clear and well-established playbook for protecting your bones while on them.

Are GLP-1 Medicines Shredding Your Bones? Here Is What the Actual Evidence Says With Dr. Susan Brian

Dr. Spencer Nadolsky and Karl sit down with Dr. Eryn Russo, a board-certified occupational and environmental medicine physician with nearly 20 years of experience working at Hill Air Force Base, where she deals with real toxic metal exposures every single day. She is one of less than one percent of all board-certified physicians practicing in this specialty, which makes her exactly the person you want explaining why the heavy metal detox content flooding your social media feed is not medicine. It is marketing.
In this episode they cover how a proper toxic exposure workup actually happens including detailed exposure history, industrial hygiene testing at the source, biological monitoring, and organ-specific testing that goes far beyond a urine panel mailed to your house, why the provoked urine test being sold by influencers is a complete artifact that artificially concentrates metals in your urine using the same chelation agent they then try to sell you as treatment, the real clinical presentations of lead, mercury, cadmium, arsenic, and chromium six and why none of them look like vague brain fog or fatigue, why the gold standard test for lead is blood not urine and what the actual diagnostic thresholds are for adults versus children, why amalgam fillings and the form of mercury previously used in vaccines are not the toxic forms people need to worry about, the Consumer Reports plant protein lead story and whether parents actually need to be concerned, why Dr. Russo has never once recommended chelation therapy in 20 years of treating workers who actually work with these chemicals daily, and why real chelation therapy carries serious renal and electrolyte risks that make unsupervised use genuinely dangerous.
The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode. Hosted by Simplecast, an AdsWizz company. See <a href="https://pcm.adswizz.com">pcm.adswizz.com</a> for information about our collection and use of personal data for advertising.

<description>&lt;p&gt;Dr. Spencer Nadolsky and Karl sit down with Dr. Eryn Russo, a board-certified occupational and environmental medicine physician with nearly 20 years of experience working at Hill Air Force Base, where she deals with real toxic metal exposures every single day. She is one of less than one percent of all board-certified physicians practicing in this specialty, which makes her exactly the person you want explaining why the heavy metal detox content flooding your social media feed is not medicine. It is marketing.&lt;/p&gt;
&lt;p&gt;In this episode they cover how a proper toxic exposure workup actually happens including detailed exposure history, industrial hygiene testing at the source, biological monitoring, and organ-specific testing that goes far beyond a urine panel mailed to your house, why the provoked urine test being sold by influencers is a complete artifact that artificially concentrates metals in your urine using the same chelation agent they then try to sell you as treatment, the real clinical presentations of lead, mercury, cadmium, arsenic, and chromium six and why none of them look like vague brain fog or fatigue, why the gold standard test for lead is blood not urine and what the actual diagnostic thresholds are for adults versus children, why amalgam fillings and the form of mercury previously used in vaccines are not the toxic forms people need to worry about, the Consumer Reports plant protein lead story and whether parents actually need to be concerned, why Dr. Russo has never once recommended chelation therapy in 20 years of treating workers who actually work with these chemicals daily, and why real chelation therapy carries serious renal and electrolyte risks that make unsupervised use genuinely dangerous.&lt;/p&gt;
&lt;p&gt;The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode.&lt;/p&gt;&lt;br/&gt; &lt;p&gt;Hosted by Simplecast, an AdsWizz company. See &lt;a href="https://pcm.adswizz.com"&gt;pcm.adswizz.com&lt;/a&gt; for information about our collection and use of personal data for advertising.&lt;/p&gt;</description>

Dr. Spencer Nadolsky and Karl sit down with Dr. Eryn Russo, a board-certified occupational and environmental medicine physician with nearly 20 years of experience treating real toxic metal exposures, to break down exactly why the heavy metal detox industry is built on tests that are not supported by any medical standard and treatments that can cause genuine harm. If an influencer has ever made you wonder whether lead, mercury, or cadmium is behind your symptoms, this is the episode that puts that fear to rest with actual science.

Heavy Metal Toxicity: Separating Real Risks From Influencer Scams | Dr. Eryn Russo

Dr. Spencer Nadolsky and Karl sit down with Dr. Adam Auton, geneticist at 23andMe, to break down a brand new paper using data from over 27,000 people that identified specific genetic variants linked to how well GLP-1 medications work and how likely someone is to experience side effects. 23andMe has over 11 million people in their research database and used voluntary survey data on medication use, dosage, duration, weight loss, and side effects to match against genetic profiles at scale, making this one of the most powerful datasets anyone has brought to this question.
In this episode they cover how genome-wide association studies work and why scanning 600,000 genetic variants at once lets researchers find signals they never could have predicted in advance, why the first signal that jumped out of the data was a variant right in the GLP-1 receptor itself and why that was the moment the team knew they were on the right track, why the same variant that predicts better efficacy also predicts a higher risk of side effects and what that tells us about how the drug is being processed, why tirzepatide users showed a separate signal in the GIP receptor that modulates side effects rather than weight loss, why carrying both variants could make someone 14 times more likely to experience side effects on tirzepatide, why genetics explains roughly 10 percent of weight loss variation and what the other 90 percent looks like, why women tend to respond better than men and why diabetics tend to respond less well, what the future of this research looks like including who regains weight after stopping and whether those patterns are genetically predictable, and why heritability is a statistical measure that gets badly misunderstood even by clinicians.
The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode. Hosted by Simplecast, an AdsWizz company. See <a href="https://pcm.adswizz.com">pcm.adswizz.com</a> for information about our collection and use of personal data for advertising.

<description>&lt;p&gt;Dr. Spencer Nadolsky and Karl sit down with Dr. Adam Auton, geneticist at 23andMe, to break down a brand new paper using data from over 27,000 people that identified specific genetic variants linked to how well GLP-1 medications work and how likely someone is to experience side effects. 23andMe has over 11 million people in their research database and used voluntary survey data on medication use, dosage, duration, weight loss, and side effects to match against genetic profiles at scale, making this one of the most powerful datasets anyone has brought to this question.&lt;/p&gt;
&lt;p&gt;In this episode they cover how genome-wide association studies work and why scanning 600,000 genetic variants at once lets researchers find signals they never could have predicted in advance, why the first signal that jumped out of the data was a variant right in the GLP-1 receptor itself and why that was the moment the team knew they were on the right track, why the same variant that predicts better efficacy also predicts a higher risk of side effects and what that tells us about how the drug is being processed, why tirzepatide users showed a separate signal in the GIP receptor that modulates side effects rather than weight loss, why carrying both variants could make someone 14 times more likely to experience side effects on tirzepatide, why genetics explains roughly 10 percent of weight loss variation and what the other 90 percent looks like, why women tend to respond better than men and why diabetics tend to respond less well, what the future of this research looks like including who regains weight after stopping and whether those patterns are genetically predictable, and why heritability is a statistical measure that gets badly misunderstood even by clinicians.&lt;/p&gt;
&lt;p&gt;The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode.&lt;/p&gt;&lt;br/&gt; &lt;p&gt;Hosted by Simplecast, an AdsWizz company. See &lt;a href="https://pcm.adswizz.com"&gt;pcm.adswizz.com&lt;/a&gt; for information about our collection and use of personal data for advertising.&lt;/p&gt;</description>

Dr. Spencer Nadolsky and Karl sit down with Dr. Adam Auton, geneticist at 23andMe, to break down a brand new paper using data from over 27,000 people that identified specific genetic variants in the GLP-1 receptor and GIP receptor that predict both how much weight someone loses on these medications and how likely they are to experience side effects. This is one of the first studies to show that precision medicine for GLP-1 drugs may already be closer than most people think.

GLP-1 Genetics: Predicting Weight Loss and Side Effects With 23andMe's Dr. Adam Auton

5:37 PM
 
 
 
 
Dr. Spencer Nadolsky and Karl sit down with Dr. Henning Langer, PhD researcher at the Charité in Berlin and founder of his own muscle metabolism lab, to break down his newly published paper combining rodent and human data to look directly at what GLP-1 medicines actually do to skeletal muscle beyond what a DEXA scan can tell you. Dr. Langer spent time at Boehringer Ingelheim specifically studying skeletal muscle during obesity and anti-obesity treatment before bringing that work to his own lab, and this paper is one of the only studies to date that has looked at muscle directly rather than lean body mass as a proxy.
In this episode they cover why the step one trial's 40 percent lean mass loss figure may not be as alarming as it sounds and why most incretin trials actually land closer to the expected 25 percent, why lean body mass on a DEXA scan conflates muscle with glycogen, liver weight, and water in ways that overstate actual muscle loss, why the mice on semaglutide that looked the roughest in their cage ran the best on the treadmill to exhaustion, what mitochondrial protein changes in the proteome data suggest about a possible fatigue resistance benefit that cannot be explained by fat loss alone, how absolute muscle force tended to drop slightly while relative strength and endurance held up, what the human data from Nottingham showed about maximum voluntary contraction and knee extension force in patients on GLP-1 treatment, why the geriatric population is the next big unanswered question in this space, and why resistance training combined with high protein still cuts muscle loss in half and remains the most powerful lever available regardless of what the pharmacology does.
The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode. Hosted by Simplecast, an AdsWizz company. See <a href="https://pcm.adswizz.com">pcm.adswizz.com</a> for information about our collection and use of personal data for advertising.

<description>&lt;p&gt; &lt;/p&gt;
&lt;p&gt;5:37 PM&lt;/p&gt;
&lt;p&gt; &lt;/p&gt;
&lt;p&gt; &lt;/p&gt;
&lt;p&gt; &lt;/p&gt;
&lt;p&gt; &lt;/p&gt;
&lt;p&gt;Dr. Spencer Nadolsky and Karl sit down with Dr. Henning Langer, PhD researcher at the Charité in Berlin and founder of his own muscle metabolism lab, to break down his newly published paper combining rodent and human data to look directly at what GLP-1 medicines actually do to skeletal muscle beyond what a DEXA scan can tell you. Dr. Langer spent time at Boehringer Ingelheim specifically studying skeletal muscle during obesity and anti-obesity treatment before bringing that work to his own lab, and this paper is one of the only studies to date that has looked at muscle directly rather than lean body mass as a proxy.&lt;/p&gt;
&lt;p&gt;In this episode they cover why the step one trial's 40 percent lean mass loss figure may not be as alarming as it sounds and why most incretin trials actually land closer to the expected 25 percent, why lean body mass on a DEXA scan conflates muscle with glycogen, liver weight, and water in ways that overstate actual muscle loss, why the mice on semaglutide that looked the roughest in their cage ran the best on the treadmill to exhaustion, what mitochondrial protein changes in the proteome data suggest about a possible fatigue resistance benefit that cannot be explained by fat loss alone, how absolute muscle force tended to drop slightly while relative strength and endurance held up, what the human data from Nottingham showed about maximum voluntary contraction and knee extension force in patients on GLP-1 treatment, why the geriatric population is the next big unanswered question in this space, and why resistance training combined with high protein still cuts muscle loss in half and remains the most powerful lever available regardless of what the pharmacology does.&lt;/p&gt;
&lt;p&gt;The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode.&lt;/p&gt;&lt;br/&gt; &lt;p&gt;Hosted by Simplecast, an AdsWizz company. See &lt;a href="https://pcm.adswizz.com"&gt;pcm.adswizz.com&lt;/a&gt; for information about our collection and use of personal data for advertising.&lt;/p&gt;</description>

Dr. Spencer Nadolsky and Karl sit down with Dr. Henning Langer, a PhD researcher at the Charité in Berlin, to break down his newly published paper combining rodent and human data to look directly at what GLP-1 medicines actually do to skeletal muscle beyond what a DEXA scan can tell you. From mice running to exhaustion on semaglutide to maximum voluntary contraction data in humans, this is the most granular conversation yet on whether these drugs are doing something to muscle that nobody fully understands yet.

Do GLP-1 Medicines Actually Cause Muscle Loss? New Research With Dr. Henning Langer

Drs. Spencer and Karl Nadolsky talk about nutrition, medicine, and fitness through the lens of two physicians who lift weights. Both doctors are former NCAA division 1 wrestlers who have gone into medicine. Dr. Spencer Nadolsky is a board certified family physician specialized in obesity medicine and lipidology. Dr. Karl Nadolsky is a board certified endocrinologist also specialized in obesity medicine.

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