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What did FLOW do with participants who could not tolerate a step?

Asked 25 May 2026Modified 21 days agoViewed 6k times
11

My records go back to the first dose with dates, so I can reconstruct the timeline exactly.

I have read the primary source rather than the summary, which has left me with more questions.

I understand the headline. I do not understand the footnotes, and the footnotes look important.

What can I legitimately conclude from this figure?

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RI
askedrukhsana_iqbal17k3725 May 2026
Add what "working" would look like for you — the answer depends on the target. – Dr_Sara_Kuusela 2 months ago
8Voting to keep this open — it is more specific than it first looks. – Dr_Yusuf_Adeyemi 6 days ago
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3 Answers

Accepted answer first, then by votes
8

Accepted answer

The short version: four-weekly steps for the weekly agents, hold rather than escalate when symptoms are active, and slower is always available.

The dose that produces an acceptable result with acceptable tolerability is the endpoint, not the top of the schedule. A substantial fraction of trial participants did well below the maximum.

Concretely, liraglutide titrates weekly rather than four-weekly because its half-life is about thirteen hours, so steady state is reached within days. The interval follows the pharmacokinetics in both cases.

Four to five half-lives to steady state is standard first-order pharmacokinetics and gives the four-week interval directly from the one-week half-life.

Nothing here is medical advice, and research-use compounds are not approved for human use.

Stepping back is a normal adjustment, not a failure.

edited 9 Jul 2026 by Dr_Nadia_Farsi — added a caveat about sampling

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answered · acceptedDr_Nadia_Farsi104k24730 Jun 2026
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3

Answering this needs the agent and the current step, since the schedules differ and the reason they differ is pharmacokinetic.

Holding a step for eight weeks instead of four is a legitimate approach with no efficacy cost at the destination, and it is what the trials effectively did for anyone who tolerated poorly.

More usefully, escalating while gastrointestinal symptoms are still active is the commonest avoidable error. Tolerance to the previous step has not developed, and the new step lands on top of it.

Trial data show gastrointestinal adverse events concentrated in the escalation phase and declining at stable doses.

The top of the schedule is not the target. The working dose is.

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DV
answeredDr_Bram_Verhoeven84k24826 Jun 2026
4Same experience here, different supplier. – juan_esquivel 10 months ago
5Two of us compared schedules and the difference was entirely in patience. – Dr_Signe_Baldursdottir 2 months ago
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1

Start with the half-life, because the interval between steps should be at least four half-lives or you are escalating before the previous step has expressed itself.

For an agent with a one-week half-life, steady state after a dose change is reached in about four to five weeks. Escalating at two weeks means escalating from a position you have not yet reached, and the resulting exposure is higher than the schedule intends.

Titrating downward is available too. Stepping back and holding is a normal adjustment rather than a failure.

Efficacy in the trials was dose-related but with substantial response at intermediate doses, which is why the maximum is not a target for everyone.

Hold rather than escalate while symptoms are active. Always.

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answeredplate_count_9k78k24826 May 2026
The arithmetic on steady state is worth doing once and remembering. – coldpack_88 30 days ago
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Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

Not medical advice. Research-use-only compounds are not approved for human use.