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.

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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.

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Dr. Spencer Nadolsky and Dr. Karl Nadolsky sit down with Dr. Stuart Phillips, senior author on the newly updated American College of Sports Medicine position stand on resistance training, to break down what 137 systematic reviews and over 30,000 participants actually tell us about building muscle, getting stronger, and improving function across the lifespan. The last version of these guidelines was published in 2009 and the science has come a long way, even if the fundamentals have not.

In this episode they cover why lifting weights twice a week is already getting most of the available benefit and three times is better but not by as much as you think, why the hypertrophy rep range is far broader than the classic 8 to 12 and what that actually means for your training, why getting stronger still requires lifting heavy things regardless of what anyone tells you, how power training is about moving with intentional velocity and why it matters more as you age than most people realize, why periodization showed no statistically significant advantage over non-periodized programs in the systematic review and what that means in practice, why eccentrically biased training produces slightly better muscle growth but is an optimization tool not a fundamental one, why time under tension does not have the evidence base people think it does, why blood flow restriction remains a niche tool rather than a strategic advantage, and why the best workout is simply the one you will actually show up and do consistently.

The Docs Who Lift podcast distills and simplifies the complexities of exercise, medicine, and weight loss. Subscribe so you never miss an episode.

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