| RetatrutidePHASE 3 | TirzepatideAPPROVED | |
|---|---|---|
| Brand names | None yet (Lilly compound LY3437943) | Zepbound, Mounjaro (and compounded versions) |
| Status | Investigational, phase 3 | FDA approved |
| Receptors | GLP-1 + GIP + glucagon | GLP-1 + GIP |
| How it works | Triple agonist. Adds glucagon receptor activity, which is believed to raise energy expenditure on top of the appetite effects. The reason for the outsized trial numbers, and part of why side effects need the larger phase 3 picture. | Dual agonist. Adds GIP receptor activity on top of GLP-1, which appears to deepen the appetite effect and may soften nausea for some people. |
| Headline trial | Phase 2 (NEJM 2023), 48 weeks, 338 adults | SURMOUNT-1, 72 weeks |
| Trial weight change | About 24% average body weight reduction at the 12 mg dose, versus about 2% on placebo. At 8 mg and above, every participant lost at least 5%. | About 21% average body weight reduction at the 15 mg dose, versus about 3% on placebo. |
| Half-life | About 6 days (reported) | About 5 days |
| Most common side effects | Gastrointestinal, dose-related, mostly mild to moderate, partially mitigated by a lower starting dose. Also a dose-dependent heart-rate increase that peaked around week 24 and declined after. | Same gastrointestinal family as semaglutide: nausea, diarrhea, vomiting, constipation, mostly during escalation and mostly mild to moderate. |
| Access and cost | Not approved, not available by prescription. Anything sold online as retatrutide is unregulated gray-market product with no pharmacy-grade verification. | Approved and widely prescribed. Zepbound self-pay vials through LillyDirect lowered the cash price for some doses. |
Trial numbers are not head-to-head. STEP-1, SURMOUNT-1 and the retatrutide phase 2 trial used different durations, doses and populations, so the percentages describe each drug in its own trial, not a race run on the same track.
The one-sentence version
Retatrutide posted the biggest numbers ever seen in a weight-loss drug trial, about 24% average reduction in 48 weeks, but it is the only one of the three you cannot be prescribed. Tirzepatide holds the best result among approved options, and semaglutide has the deepest long-term evidence base, including cardiovascular outcomes data. Which one is relevant to you mostly depends on whether you are choosing a medication with your prescriber this year or watching where the field goes next.
Approval status, August 2026
Semaglutide and tirzepatide are FDA approved and prescribable. Retatrutide is not: it is in Eli Lilly’s phase 3 TRIUMPH program, and no approval date exists. Searches for “retatrutide approval status” spike every time a trial reads out, and the honest answer is always the same: when it changes, it will be everywhere at once. Any site quoting you a confident month is guessing.
About the gray market: because the phase 2 numbers were spectacular, an entire online economy now sells “retatrutide” as a research chemical. None of it is pharmacy-grade, none of it is verified for dose or purity, and none of it comes with the trial’s monitoring, which matters for a drug whose safety picture, including a dose-dependent heart-rate increase, is exactly what phase 3 exists to settle. A spectacular trial result is not the same thing as a safe vial from an unregulated vendor.
What “better” actually means
The receptor count makes a tidy story: each added receptor, on average, deepened trial weight loss. But a molecule is not better in the abstract; it is better for a person with a body, a budget, and an insurance plan. An approved drug with multi-year safety data, coverage pathways, and a pharmacy behind it beats a bigger number that you cannot legally or safely obtain. If your real question is “should I be on something different,” that is a prescriber conversation, and it goes better with structure: what you are on, what it is doing to your trend, and what problem a switch would solve.
Where the clearance math fits
All three are weekly injections with half-lives between 5 and 7 days, which means the same washout arithmetic applies to a missed dose, a supply gap, or stopping: levels fall by half roughly every week, appetite returns along that curve, and nothing dramatic happens on day one. The washout calculator draws your personal curve, and the taper visualizer shows what published step-down patterns look like. If the question behind your comparison is really about life after the medication, start with do you have to take these drugs forever and what a maintenance dose actually means.