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Retatrutide Just Beat Ozempic. What I Tell Patients Who Ask for It
Originally published on Substack.
Double the weight loss. Here’s what the press release leaves out.
In a new head-to-head trial, people with type 2 diabetes on retatrutide lost about 21% of their body weight. On the highest approved dose of Ozempic, they lost about 9%.
I’m a cardiologist. If you ask me about it, here’s what I’ll tell you, and what the press release leaves out.
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The headline is real
On October 28, Eli Lilly released top-line results from TRANSCEND-T2D-2, a Phase 3 trial. It randomized 1,298 adults with type 2 diabetes, already on metformin, to retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg for 80 weeks. They started at about 226 pounds, with an average A1C of 8.3%.
Retatrutide works on three hormone receptors: GLP-1, GIP and glucagon. Ozempic works on one.
The results: A1C fell 2.2 points on both retatrutide doses versus 1.8 on Ozempic. Weight fell 19.5% and 20.9% versus 9.4%. On the top dose, that’s about 47 pounds versus 21.
That is a big gap. Now the fine print.
What the press release doesn’t tell you
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It’s a press release. No peer review, no full data. Lilly says details will come at a future medical meeting.
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It was open-label. Everyone knew which drug they were on. Weight and A1C are hard numbers, but behavior can still shift.
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The numbers assume everyone stayed on the drug. Lilly reported the “efficacy estimand.” Results that count the people who stopped will likely be smaller.
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More people quit. Stopping for side effects: 4.8% and 7.9% on retatrutide versus 2.7% on Ozempic. Dysesthesia, an abnormal skin sensation, ran 4.8% and 6.5% versus 2.7%. Nausea was similar in all three groups, about 21% to 24%.
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There is no heart data yet. Ozempic’s active ingredient has it. In SELECT (NEJM, 2023), 17,604 adults with heart disease and overweight, without diabetes, took semaglutide 2.4 mg or placebo. Heart attack, stroke or cardiovascular death fell from 8.0% to 6.5%. Retatrutide has no heart outcomes results yet.
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It isn’t approved. Lilly calls it investigational. No regulator anywhere has approved it.
Is it the drug, or just the weight loss?
This is the smartest question about retatrutide. The plain answer: we can’t tell yet. The top-line release doesn’t separate the two. Full data will help with blood sugar. For the heart, only an outcomes trial will answer it.
The part that worries me
There is no legal retatrutide for sale. Yet it’s sold online as “research use only.”
Two deaths were reported this year to the FDA’s adverse event system in people who took black-market or compounded retatrutide, according to CBS News reporting summarized by the Partnership for Safe Medicines. Both products were likely bootleg. Causation has not been established. But you can’t know what is in an unregulated vial, or how much.
What I tell patients (save this)
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Don’t buy it online. Ever. Not “research grade,” not from a clinic that can’t show you an FDA-approved label.
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If you qualify now, don’t wait. Approved GLP-1 drugs exist today. Ask your doctor which one fits you.
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Protect your muscle. On any of these drugs, ask about enough protein and resistance training.
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Know the side effects. Nausea and diarrhea are common. Call if you can’t keep fluids down.
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Ask for heart data, not just weight data. A drug that lowers the scale is good. A drug proven to prevent heart attacks is better.
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The deeper point
Weight is a number. A longer, stronger life is the goal. The best medicine is the one with proof that it gets you there, from a source you can trust. Patience is part of the treatment.
If retatrutide were approved tomorrow, would you switch, or wait for the heart-outcomes data? Tell me in the comments.
This is education, not medical advice.
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Blessings.
Afshine Ash Emrani, M.D., F.A.C.C.
Assistant Clinical Professor, UCLA
David Geffen School of Medicine
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