Uploaded August 2026 | Updated September 2026, 1 week ago
GLP-1 drugs don't rev your metabolism. They lean on the same appetite circuit leptin uses, through a brainstem backdoor that survived this patient's surgery. Then the drug built for exactly this problem, setmelanotide, and the trial and approval that changed the answer this year.
Timestamps:
00:00:00 Why GLP-1 drugs still worked: the brainstem backdoor
00:01:41 Responders and non-responders
00:05:10 Setmelanotide: a drug for the broken circuit
00:06:23 TRANSCEND, and the new FDA approval
Resources:
Barbell Medicine coaching and templates: barbellmedicine.com
Plus podcast subscription: barbellmedicine.com/shop/subscriptions/plus-podcast-subscription
Barbell Medicine Premium: barbellmedicine.com/shop/subscriptions/barbell-medicine-premium
Signal (book pre-order): barbellmedicine.com/shop/learning/signal
Our Protein Content:
barbellmedicine.com/blog/protein-and-weight-loss
barbellmedicine.com/blog/protein-on-ozempic
barbellmedicine.com/blog/barbell-medicine-protein-recommendations
Studies
Levine et al. Cell Metabolism 2014. doi:10.1016/j.cmet.2014.02.006
Naghshi et al. BMJ 2020. doi:10.1136/bmj.m2412
Devries et al. J Nutr 2018. doi:10.1093/jn/nxy197
Antonio et al. J Nutr Metab 2016. doi:10.1155/2016/9104792
Knight et al. Ann Intern Med 2003. doi:10.7326/0003-4819-138-6-200303180-00009
Klahr et al. (MDRD). NEJM 1994. doi:10.1056/NEJM199403313301301
Hahn, Hodson & Fouque. Cochrane 2020. doi:10.1002/14651858.CD001892.pub5
Obeid, Hiremath & Topf. Kidney360 2022. doi:10.34067/KID.0001002022
Lew et al. J Am Soc Nephrol 2017. doi:10.1681/ASN.2016030248
Castaneda et al. Ann Intern Med 2001. doi:10.7326/0003-4819-135-11-200112040-00008
Bauer et al. (PROT-AGE). JAMDA 2013. doi:10.1016/j.jamda.2013.05.021
Fenton et al. Nutrition Journal 2011. doi:10.1186/1475-2891-10-41
Shams-White et al. Am J Clin Nutr 2017. doi:10.3945/ajcn.116.145110
Witard et al. Am J Clin Nutr 2013. doi:10.3945/ajcn.112.055517
Macnaughton et al. Physiol Rep 2016. doi:10.14814/phy2.12893
Trommelen et al. Cell Reports Medicine 2023. doi:10.1016/j.xcrm.2023.101324
Wycherley et al. Am J Clin Nutr 2012. doi:10.3945/ajcn.112.044321
Moore et al. JAMA Intern Med 2016. doi:10.1001/jamainternmed.2016.1548
Larsson et al. Cancer Med 2020. doi:10.1002/cam4.3345
Brenner, Meyer & Hostetter. NEJM 1982. doi:10.1056/NEJM198209093071104
Chan et al. PLoS One 2011. doi:10.1371/journal.pone.0020456
Berryman et al. Am J Clin Nutr 2018. doi:10.1093/ajcn/nqy088
Morton et al. Br J Sports Med 2018. doi:10.1136/bjsports-2017-097608
GLP-1 drugs don't rev your metabolism. They lean on the same appetite circuit leptin uses, through a brainstem backdoor that survived this patient's surgery. Then the drug built for exactly this problem, setmelanotide, and the trial and approval that changed the answer this year.
Timestamps:
00:00:00 Why GLP-1 drugs still worked: the brainstem backdoor
00:01:41 Responders and non-responders
00:05:10 Setmelanotide: a drug for the broken circuit
00:06:23 TRANSCEND, and the new FDA approval
Resources:
Barbell Medicine coaching and templates: barbellmedicine.com
Plus podcast subscription: barbellmedicine.com/shop/subscriptions/plus-podcast-subscription
Barbell Medicine Premium: barbellmedicine.com/shop/subscriptions/barbell-medicine-premium
Signal (book pre-order): barbellmedicine.com/shop/learning/signal
Our Protein Content:
barbellmedicine.com/blog/protein-and-weight-loss
barbellmedicine.com/blog/protein-on-ozempic
barbellmedicine.com/blog/barbell-medicine-protein-recommendations
Studies
Levine et al. Cell Metabolism 2014. doi:10.1016/j.cmet.2014.02.006
Naghshi et al. BMJ 2020. doi:10.1136/bmj.m2412
Devries et al. J Nutr 2018. doi:10.1093/jn/nxy197
Antonio et al. J Nutr Metab 2016. doi:10.1155/2016/9104792
Knight et al. Ann Intern Med 2003. doi:10.7326/0003-4819-138-6-200303180-00009
Klahr et al. (MDRD). NEJM 1994. doi:10.1056/NEJM199403313301301
Hahn, Hodson & Fouque. Cochrane 2020. doi:10.1002/14651858.CD001892.pub5
Obeid, Hiremath & Topf. Kidney360 2022. doi:10.34067/KID.0001002022
Lew et al. J Am Soc Nephrol 2017. doi:10.1681/ASN.2016030248
Castaneda et al. Ann Intern Med 2001. doi:10.7326/0003-4819-135-11-200112040-00008
Bauer et al. (PROT-AGE). JAMDA 2013. doi:10.1016/j.jamda.2013.05.021
Fenton et al. Nutrition Journal 2011. doi:10.1186/1475-2891-10-41
Shams-White et al. Am J Clin Nutr 2017. doi:10.3945/ajcn.116.145110
Witard et al. Am J Clin Nutr 2013. doi:10.3945/ajcn.112.055517
Macnaughton et al. Physiol Rep 2016. doi:10.14814/phy2.12893
Trommelen et al. Cell Reports Medicine 2023. doi:10.1016/j.xcrm.2023.101324
Wycherley et al. Am J Clin Nutr 2012. doi:10.3945/ajcn.112.044321
Moore et al. JAMA Intern Med 2016. doi:10.1001/jamainternmed.2016.1548
Larsson et al. Cancer Med 2020. doi:10.1002/cam4.3345
Brenner, Meyer & Hostetter. NEJM 1982. doi:10.1056/NEJM198209093071104
Chan et al. PLoS One 2011. doi:10.1371/journal.pone.0020456
Berryman et al. Am J Clin Nutr 2018. doi:10.1093/ajcn/nqy088
Morton et al. Br J Sports Med 2018. doi:10.1136/bjsports-2017-097608
