The 'Toxic' Peptide That Just Broke Every Obesity Record

Brad Stanfield

Apr 21, 2026

Episode description

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Timestamps:
00:00 Glucagon's Role in Obesity and Diabetes
02:49 The Discovery of GLP-1 and GIP
04:44 Results of the New Retatrutide Trial
06:45 Side Effects of Retatrutide
08:59 The Importance of Protein Intake

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Here are the links to the research papers referenced in the video:
https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average — TRIUMPH-4 press release
https://pmc.ncbi.nlm.nih.gov/articles/PMC5805853/ — Glucagon discovery (Peptides 2018)
https://journals.lww.com/jodb/fulltext/2023/11001/historical_perspectives_of_glucagon_s_discovery.4.aspx — Glucagon history (JODB 2023)
https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.12958 — LY2409021 glucagon antagonist trial
https://pmc.ncbi.nlm.nih.gov/articles/PMC4509428/ — GLP-1 receptor agonists review
https://www.prnewswire.com/news-releases/novo-nordisk-receives-fda-approval-of-ozempic-semaglutide-injection-for-the-treatment-of-adults-with-type-2-diabetes-300567052.html — Ozempic FDA approval
https://www.nejm.org/doi/full/10.1056/NEJMoa2032183 — Semaglutide STEP 1 (NEJM 2021)
https://pmc.ncbi.nlm.nih.gov/articles/PMC12507501/ — Tirzepatide dual agonist review
https://www.nejm.org/doi/full/10.1056/NEJMoa2206038 — SURMOUNT-1 tirzepatide (NEJM 2022)
https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-achieved-157-weight-loss-adults-obesity-or — SURMOUNT-2 press release
https://pmc.ncbi.nlm.nih.gov/articles/PMC3609580/ — GLP-1 + glucagon co-infusion
https://insights.som.yale.edu/podcasts/health-veritas/ania-jastreboff-treating-obesity-without-shame — Jastreboff Yale podcast
https://www.nejm.org/doi/full/10.1056/NEJMoa2301972 — Retatrutide Phase 2 (NEJM 2023)
https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-demonstrated-significant-reductions-in-a1c-and-weight-in-first-phase-3-trial-for-treatment-of-type-2-diabetes-302718589.html — TRANSCEND-T2D-1 press release
https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisks-obesity-drug-falls-short-against-eli-lillys-copenhagen-trial-2026-02-23/ — Reuters: CagriSema vs Zepbound
https://my.clevelandclinic.org/health/symptoms/24989-dysesthesia — Cleveland Clinic: dysesthesia
https://www.usatoday.com/story/life/health-wellness/glp-1-cost/88513308007/ — USA Today: GLP-1 drug costs
https://www.cbsnews.com/boston/news/blue-cross-blue-shield-massachusetts-weight-loss-glp1/ — BCBS Massachusetts drops GLP-1 coverage
https://www.bmj.com/content/392/bmj-2025-085304 — Weight regain after stopping (BMJ 2025)

Thumbnail by James Kelly
Video edited by Troy Young
Script by John Milliken

The links above are affiliate links, so I receive a small commission every time you use them to purchase a product. The content contained in this video, and its accompanying description, is not intended to replace viewers’ relationships with their own medical practitioner. Always speak with your doctor regarding the content of this channel, and especially before using any products, services, or devices discussed on this channel.

Mindsip insights from this episode:

Prevent muscle loss during rapid weight loss with resistance training and protein

A huge potential downside of such rapid weight loss is losing significant amounts of muscle unless the person performs resistance exercise and eats enough protein.

#muscle

#weight-loss

Address unintended weight loss from Retatrutide use

A unique clinical problem has emerged where patients on the new drug Retatrutide are stopping the medication because they are losing more weight than they intended.

#GLP1

#weight-loss

Activate glucagon with GLP-1 to enhance metabolism

When glucagon is activated alongside GLP-1, it becomes a metabolic accelerator that burns energy, while the GLP-1 simultaneously prevents the blood sugar spike glucagon would normally cause.

#GLP1

#metabolism

Utilize Retatrutide as first triple-hormone receptor agonist for health benefits

The new drug, Retatrutide, is the first triple-hormone receptor agonist, turning on GLP-1, GIP, and the once-feared glucagon all at once.

#GLP1

Leverage glucagon as a breakthrough in weight loss solutions

The hormone glucagon, once called the 'toxic fraction' because it raised blood sugar and was suppressed for decades, is now a key component of a breakthrough weight loss drug.

#hormones

#weight-loss

Achieve continuous weight loss with Retatrutide's groundbreaking results

Unlike all previous obesity drugs that show a plateau, the weight loss curve for Retatrutide was still trending down at the end of the 48-week trial, a first in obesity pharmacology.

#obesity

#weight-loss

Recognize dysesthesia as a potential side effect of high-dose treatment

A novel side effect called dysesthesia, an abnormal sense of touch described as 'skin on fire' or 'lightning bolts,' was reported by one in five patients on the highest dose.