Eli Lilly put its experimental triple-acting shot up against the highest approved dose of Ozempic. By Lilly's own count, people on it lost more than twice as much weight. By Lilly's own count. Hold on to that phrase, it's going to get a workout today. This is GLP-1 Daily for Thursday, October 29. After the retatrutide results, Health Secretary Robert F. Kennedy Jr. clears the way for pharmacies to compound six unapproved peptides, and a study out of Nebraska looks at what is actually being mixed into compounded semaglutide and tirzepatide.
Jonathan Gardner, senior reporter at BioPharma Dive:
Those benefits appear to come with a trade-off. In the study, only 3% of Ozempic recipients stopped treatment because of side effects compared with 8% of the people on the highest retatrutide dose and 5% of those in the 9 mg group.
The benefits first. Lilly announced topline results Wednesday from TRANSCEND-T2D-2, a phase 3 trial in 1,298 adults with type 2 diabetes that metformin wasn't controlling. After 80 weeks, both retatrutide doses lowered A1C by an average of 2.2 points, versus 1.8 on Ozempic 2 milligrams. Average weight loss was about 20 to 21 percent on retatrutide and about 9 percent on Ozempic. Now the fine print, which Cassidy was going to insist on anyway. Every number here is company-reported, from a press release, with no journal paper yet. The trial was open-label, so people knew which drug they were on. And the figures assume everyone stayed on their assigned drug for the full 80 weeks. I was, yes. Side effects were mostly gastrointestinal, led by diarrhea and nausea. Also, this was against Ozempic, not Lilly's own Zepbound; that head-to-head is still running. And as The National News Desk pointed out, the study didn't show whether retatrutide reduces heart attacks or strokes. Lilly plans to seek FDA approval in early 2027, according to The National News Desk. Until then, Lilly's release says anyone selling retatrutide to consumers is breaking the law. We covered that black market on October 23, including a bodega vial that CBS found contained no peptide at all. If you're wondering whether a stronger drug is right for you, ask your prescriber, not a website.
Berkeley Lovelace Jr., writing for NBC News:
In a notice filed Wednesday, the agency said it would exercise “enforcement discretion,” meaning it will not take legal action against compounding pharmacies that make the six unapproved peptides. In practice, that means these pharmacies can start offering them now, even though the peptides aren’t yet on the Food and Drug Administration’s list of ingredients compounding pharmacies are allowed to make.
The six are BPC-157, epitalon, KPV, MOTS-c, semax and TB-500. They're promoted online for everything from faster healing to a longer lifespan. None is FDA-approved, and NBC reports the FDA's own scientists concluded there isn't enough data to show they're safe and effective. To be clear, semaglutide, tirzepatide and retatrutide are not on the list. It belongs here because it runs through the same compounding system this show keeps covering. According to the law firm BakerHostetler, it covers 503A pharmacies filling patient-specific prescriptions, not 503B outsourcing facilities or research chemicals. Pharmacies must use an FDA-registered ingredient maker, test what they get, put only one listed peptide in each product, and report serious side effects to MedWatch. The two sides are far apart. Kennedy wrote that the policy advances patient choice while protecting safety. Peter Lurie, a former FDA official who now runs the Center for Science in the Public Interest, told NBC the FDA was essentially turning a blind eye. And MedPage Today reports FDA scientific staff opposed the change. HHS filed the notice Wednesday, and it's set for formal publication tomorrow. CBS reports public comment runs through November 13. HHS itself says the policy doesn't establish that these products are safe or effective. Testing tells you what's in the vial, not whether it works. If a wellness clinic offers you one alongside your GLP-1, check with your prescriber first.
Marilynn Larkin, writing for Medscape Medical News:
Compounded GLP-1s contain ingredient combinations not found in FDA-approved products, introducing uncertainty about composition, purity, and potency, according to a new study. The authors argue this warrants mandatory testing and adverse-event reporting for mass-compounded combination drugs.
The study, in JAMA, uses Nebraska's prescription monitoring program, the first in the country to capture every dispensed prescription, compounded ones included. Before 2024 there were no compounded GLP-1 prescriptions in the data. By 2025, semaglutide and tirzepatide made up 86 percent of compounded weight-loss prescriptions, and 99.5 percent of those prescriptions were paid in cash. Two-thirds of compounded tirzepatide prescriptions contained at least one form of vitamin B12. Levocarnitine use climbed to 16 percent in 2025. The authors suggest compounders may have been trying to make products they could argue are clinically distinct from approved tirzepatide after the FDA declared that shortage resolved in December 2024. Lead author Joseph Mattingly of the University of Utah says there's little clinical evidence behind the energy and anti-nausea claims for those add-ins. He adds that the combinations get no premarket testing and carry no adverse-event reporting requirement. Caveats: it's one state, and the records show what was dispensed, not what was in the vial or how patients did. All of these came from out-of-state pharmacies, three in Florida and Texas filling nearly 70 percent, so it isn't a verdict on compounders in general. Medscape lists Mattingly's outside fees, from groups including PhRMA, but doesn't name who funded the study. If you're on a compounded product, tell your prescriber exactly what's in it. And if something goes wrong, Mattingly says to report it to FDA MedWatch.
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So that's Thursday: a big company claim, a big policy fight, and a closer look at what's inside compounded vials. None of it is medical advice, so bring your questions to your own clinician. GLP-1 Daily is a Lantern Podcast, and we're back with you tomorrow.