IGF-1 as a surrogate endpoint and its limitations

IGF-1 as a surrogate endpoint and its limitations Writing it up because I had to work it out twice and would rather nobody else did.

IGF-1, and specifically the version of it that the documentation does not cover. The maintained page handles the general case well and stops exactly where my question starts.

Setting out the gap in case it is a gap in the page rather than a gap in what is known.

Adding the measurement that the opening post says would settle it.

Reconstitution volumes in this family are often small enough that dead volume in the syringe is a meaningful fraction of the dose. A fixed-needle insulin syringe is worth the trouble here specifically.

The strength of my opinion here exceeds the strength of my evidence.

The confident answers on IGF-1 and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.

What a well-designed human trial of a secretagogue would look like: randomised, placebo-controlled, adequate sample size, IGF-1 as primary outcome, muscle and strength as secondary outcomes, adequate follow-up duration. Very few secretagogue trials meet that description.

Flagging that the sources on this are thinner than the confidence in the thread suggests.

On the opening post — agreed on the reasoning, with one qualification.

Effects reported at the level of appetite are the most consistently described and the most mechanistically direct for the ghrelin-receptor compounds, which is not what most people are taking them for.

That is clearer than the version I had in my head. Thank you.

Pulsatile secretion matters because growth hormone is secreted in pulses, not continuously. A single post-dose growth hormone level is nearly uninterpretable. Assessing this class properly requires serial sampling or an integrated measure like IGF-1, and almost nothing published online does either.

I would rather be precise about what I do not know than vague about what I do.

Confirming post #5 from a second method, which matters more than confirming it from a second person.

IGF-1 as a surrogate: it is a better integrated measure than a spot growth hormone level and it is still a surrogate, with all the caveats that come with surrogates. Stable or rising IGF-1 is not the same as "this is working" in any health-related sense.

The literature is thinner on this than the confidence in the thread implies.

Published human data on most of this family is thin, old, or from small studies with surrogate endpoints. That is a genuine limitation and it is the honest answer to most questions in this subcategory.

IGF-1 as a downstream marker is more informative than a single growth hormone measurement because it integrates over a longer period. It is still a proxy, and proxies in this area have a mixed record.

I would rather say I do not know than round it up to an answer.