The evidence status here should be stated in the first line of any post about it rather than the last. Everything is phase 2 or earlier, and a reader arriving from a search will not know that unless somebody says so. A single observation, in a thread that deserves better than single observations.
On the subject in the title: Retatrutide phase 2 in type 2 diabetes: the Lancet paper Working notes rather than a conclusion.
Asking about retatrutide phase 2 in type on behalf of the question I keep seeing asked badly, including by me.
Framed properly it is answerable. Framed the usual way it is not, and that is most of why the previous threads went nowhere.
Picking up the opening post: that is the part I would want checked first.
Anyone deciding on the basis of what is published should know that what is published is a phase 2 programme and some pharmacokinetics. That is a genuinely early evidence base and this page will say so until it changes.
I would be glad to be shown a cleaner way of putting this.
The evidence status here should be stated in the first line of any post about it rather than the last. Everything is phase 2 or earlier, and a reader arriving from a search will not know that unless somebody says so.
A single observation, in a thread that deserves better than single observations.
Coming back to post #4, because the follow-up matters more than the original answer.
Mass and identity: a report on retatrutide should state the mass detected by LC-MS, not assume a theoretical mass. The theoretical mass is not published in peer-reviewed literature for retatrutide at present.
Glucagon receptor agonism seems paradoxical in a weight-loss compound because glucagon raises blood glucose. The paradox resolves because glucagon agonism also increases energy expenditure and promotes hepatic fat oxidation, and the incretin components offset the glycaemic effect. In diabetes trials, HbA1c improved rather than worsened.
A guess, clearly labelled as one.
Glycaemic effects improved rather than worsened in the diabetes work despite the glucagon component, which is the observation that resolves the apparent paradox. It is worth understanding that mechanism before repeating either half of it.
Happy to be corrected if someone holds better data than mine.
Retatrutide is investigational. Anything obtained outside a trial is by definition research-use-only material with no human-use authorisation. This site will state that plainly rather than winking at it.
I would hold that lightly until someone with a larger sample weighs in.
Retatrutide is investigational. Material obtained outside a clinical trial is research-use-only by definition, is not approved for human use, and carries no assurance about its identity or content beyond whatever independent testing you commission yourself.
I would call that likely rather than established.
Following this. I have the same question and no better information than the first post.
Post #11 and I disagree about the size of the effect, not about the direction.
The phase 2 obesity paper reported dose-dependent weight reduction of a magnitude that attracted attention. It also reported dose-dependent heart-rate increases. The heart-rate signal is the reason phase 3 exists rather than something assumed negligible based on phase 2.
If the premise is wrong, everything after it is decoration.
Why this subcategory is more cautious than elsewhere: retatrutide is investigational, phase 3 is ongoing, and the heart-rate signal in phase 2 is not negligible. Caution is proportionate to the evidence status.
Nausea and vomiting were dose-related in the phase 2 work, as they are throughout this class. What is not established is whether the tolerability profile differs from the dual agonists at equipotent effect, because equipotence has not been established either.
Dose-response in the phase 2 obesity work was clear across the studied range, with no obvious plateau within it. Extrapolating beyond the highest studied dose from that is exactly the reasoning trials are designed to prevent.
Post #15 put the caveat in the right place and I want to underline it.
Triple agonism: is the effect additive, synergistic, or neither? A phase 2 comparison of tirzepatide (dual) to retatrutide (triple) would answer that question. The published data does not include such a direct comparison.
If anyone can point at the primary source I would be grateful.
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