cjc 1295 dac vs no dac, is the half life really the whole story?

pulsatile_releaseAnalyst

Trying to state this cleanly because the naming is a mess.

CJC-1295 with DAC has a drug affinity complex that binds albumin. Half life goes from minutes to days.

CJC-1295 without DAC is basically Mod GRF(1-29), a short acting GHRH analog. Half life measured in minutes.

So with DAC you get a sustained elevation, no DAC you get something closer to a pulse. GH release is naturally pulsatile, and the argument for the short version is that it preserves that pattern instead of flattening it.

What I can't resolve from the literature: does the pulsatile pattern actually matter for anything people care about? It matters a lot in the underlying GH physiology. Whether it matters for outcomes is a different question and I don't think it's settled.

The half life numbers are solid. The "pulsatility matters so short acting is better" step is inference, not a demonstrated outcome difference. Am I wrong?

15 replies11 upvotesPeptide Comparisons

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15 replies

  • GHaxisSenior Analyst

    You're not wrong. The physiology is solid, sustained GHRH signaling does downregulate. But "downregulation happens" and "therefore outcome X differs" are two separate claims and only the first one is established.

    9 upvotes

  • same_tbhSenior Analyst

    the naming really is a mess

    3 upvotes

  • PKcurveSenior Analyst

    Numbers since that's the useful part:

    no DAC / Mod GRF: roughly 30 min with DAC: roughly 6-8 days, albumin bound

    Two orders of magnitude. Everything downstream follows from that.

    11 upvotes

    • ShowMeTheDataSenior Analyst

      Source for the 6-8 day figure?

      3 upvotes

    • pulsatile_releaseAnalyst

      Thanks, wasn't confident enough in the ranges to put them in the post.

      3 upvotes

    • decimal_placesSenior Analyst

      Approximate though. Order of magnitude is the reliable bit.

      2 upvotes

  • newvialwhodisSenior Analyst

    wait is mod grf and no-dac cjc the same thing or just similar?

    4 upvotes

    • GHaxisSenior Analyst

      Same molecule, different names. You'll see them sold as separate products which causes endless confusion.

      7 upvotes

    • newvialwhodisSenior Analyst

      ok that explains a lot

      2 upvotes

  • deload_weekAnalyst

    so dac = long, no dac = short. got it

    2 upvotes

  • effect_size_plsSenior Analyst

    The pulsatility argument gets repeated like it's settled. It's a prior. A decent one. I have never seen a head to head measuring an actual downstream difference.

    5 upvotes

    • mechanism_firstSenior Analyst

      I'd defend the prior harder than that. Receptor desensitization under sustained agonism is well characterized in general, it's not a handwave.

      4 upvotes

    • effect_size_plsSenior Analyst

      Agreed it's the better prior. My objection is to it being stated as a finding.

      3 upvotes

  • quick_qSenior Analyst

    which one has more research behind it?

    1 upvote

    • pulsatile_releaseAnalyst

      Depends what you count. The short acting side inherits a much older GHRH literature.

      3 upvotes

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