CJC-1295 with and without DAC: what the modification does — what changed since

CJC-1295 with and without DAC: what the modification does — what changed since Writing it up because I had to work it out twice and would rather nobody else did.

Comparing SURMOUNT-OSA (N Engl J Med, 2024) with SUSTAIN 6 (N Engl J Med, 2016) and finding the comparison harder than it looks.

Different populations, different durations, different endpoints defined slightly differently, and in one case a different estimand. People compare the headline percentages anyway, including me until recently.

Is there a defensible way to put these side by side, or is the honest answer that there is not and we should stop?

the opening post is right about the mechanism and I think understates the practical bit.

Secretagogues and glucose tolerance: there is a mechanistic concern that sustained growth hormone elevation might impair glucose tolerance. The clinical relevance of this concern in practice is not well established.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

Development history is more informative than speculation: ipamorelin was investigated clinically for post-operative ileus and was not taken forward to registration. That it was not brought to market tells you something about the cost-benefit calculation that any amount of forum enthusiasm does not.

Ipamorelin selectivity claims originate in preclinical characterisation and are reasonably well supported for what they claim: less effect on cortisol and prolactin than earlier GHRPs. Whether that translates to something clinically meaningful is a different question from whether the selectivity is real.