The drugs being talked about before they are drugs

What this comes down to

• Retatrutide's phase 2 trial enrolled 338 adults with obesity. At 48 weeks, least-squares mean weight change was -24.2% at 12 mg against -2.1% on placebo. Six randomized trials of it are indexed in total.
• Orforglipron is the further along of the two and the smaller number: a phase 3 trial of 3,127 patients reported -11.2% at 36 mg against -2.1% on placebo at 72 weeks. It is a small molecule, not a peptide, which is why it can be a tablet.
• No seller on our roster prices any of these molecules today, and the pattern we used covers retatrutide, cagrilintide, survodutide, mazdutide, orforglipron, amycretin and tesofensine. The same kind of pattern found semaglutide on 213 of the 257 sellers we have read.
• A drug with no approval has no approved indication, no approved dose and no FDA-reviewed labeling. Whatever is in a vial sold under one of these names, nothing has reviewed what it is.

Retatrutide: the biggest number, and the earliest phase

The phase 2 trial enrolled 338 adults with obesity. At 24 weeks, least-squares mean percent weight change was -7.2% at 1 mg, -12.9% at 4 mg, -17.3% at 8 mg and -17.5% at 12 mg, against -1.6% on placebo. At 48 weeks those became -8.7%, -17.1%, -22.8% and -24.2%, against -2.1%. At 12 mg, every participant lost at least 5%, 93% lost at least 10% and 83% lost at least 15%^[1]. The adverse events were gastrointestinal and dose-related, and the trial reports dose-dependent increases in heart rate that peaked at 24 weeks and then declined.

Orforglipron: further along, and a tablet on purpose

Orforglipron is a small-molecule, non-peptide GLP-1 receptor agonist, which is the whole point of it: a small molecule survives the gut, so it can be a once-daily tablet without the absorption enhancer and the empty-stomach ritual that the approved oral semaglutide requires. Its phase 3 obesity trial randomized 3,127 patients without diabetes across 6 mg, 12 mg, 36 mg and placebo for 72 weeks. Mean weight change was -7.5%, -8.4% and -11.2% against -2.1% on placebo, and adverse events led to discontinuation in 5.3% to 10.3% of treated patients against 2.7% on placebo^[2].

Set that beside the head-to-head result and the ordering is clear enough: the approved injections are still the larger effect. SURMOUNT-5 reported -20.2% and -13.7% at 72 weeks for the two approved injectables^[5]. An 11.2% oral result is a real drug and a different product, and the reason to want it is convenience rather than magnitude. Neither molecule has an approved product of any kind: asked for a brand name by either ingredient, the openFDA label API returns nothing, while returning six spellings for tirzepatide and four for semaglutide in the same session^[3]. Six randomized trials stand behind retatrutide and seventeen behind orforglipron^[4].

retatrutide[tiab] AND "randomized controlled trial"[pt] AND "humans"[mh]

Nobody on our roster prices one, which is the answer we want

Across the 257 sellers on our price roster, not one publishes a priced line for any of these seven molecules. That is the right answer and it is not a guaranteed one: the same kind of pattern, run in the same pass, found semaglutide on 213 sellers, so the zero is a fact about the menu rather than a broken search. Where these molecules do appear is the research-chemical market, sold by the milligram with no prescription and no pharmacy, and that market is outside everything our grading method can see.

• An unapproved molecule has no approved dose. Every number on a vial of it is somebody's choice, not a reviewed one.
• Phase 2 numbers shrink. Compare like with like: 48-week phase 2 against 72-week phase 3 is not a comparison.
• Ask what is actually in the vial and who tested it. What third-party testing proves is the article about how little a certificate on a website establishes.
• If a seller offers you one of these by name, that tells you something about the seller regardless of the molecule. Where compounded semaglutide stands with the FDA sets out what the rules for an unapproved bulk substance are.

Questions people actually ask