Topic summary

Where the four-week escalation interval comes from, and what it is not

Practice › Dosing & titration missed dose semaglutide tirzepatide titration dose reduction Solved

This is a generated summary. It shows the 9 most-liked posts from a topic of 61, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.

w.verhoevenTL2 Moderator Solution20 May 2024#3

Norrington, post #2: When a dose reduction is the correct response to a side effect: if a side effect is dose-dependent (nausea, constipation, injection discomfort), reducing the dose is a reasonable response. If the side effect is not dose-dependent (e.g., hypoglycemia with insulin), dose reduction does not address the issue. Go to post

Micro-titration: the concept of increments smaller than the labelled steps. It has no evidence base from trials but is described by some people. The downside is that very small increments are hard to measure accurately with a syringe.

7 likes in reply to #2 2.2y

i.ilungaTL2 Moderator27 May 2024#7

post #6 is right about the mechanism and I think understates the practical bit.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

27 likes 2.2y

k.radichTL2 Moderator1 Jun 2024 · edited#11

Holding a dose indefinitely: the trials did not study indefinite holding at a non-maximum dose. The trials escalated to a target and then held that. What happens if you stay at an intermediate dose for years is not formally studied and extrapolation is the best available reasoning.

28 likes 2.2y

buffer_reviewTL3Regular13 Jun 2024#20

post #19 answers the question as asked. The question underneath it is different.

How the published trials escalated: they used specific step sizes and intervals. The STEP programme used a particular cadence; the SURPASS and SURMOUNT programmes used slightly different ones. Reading them side by side shows the variation is real but small.

27 likes 2.1y

c.vermeulenTL2 Moderator16 Jun 2024 · edited#22

s.grigorescu, post #6: Splitting a weekly dose in two: the pharmacokinetic argument against is that you want the benefit of long half-life, which gives a slowly changing plasma level from a weekly dosing schedule. Splitting it flattens the curve further but loses the convenience of once-weekly dosing. The trade-off is convenience versus a slightly flatter… Go to post

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

23 likes in reply to #6 2.1y

s.solbergTL2 Moderator21 Jun 2024#27

Picking up post #24: that is the part I would want checked first.

Stepping down deliberately: the withdrawal trials show that stopping is followed by regain. The step-down literature is thinner. The conservative assumption is that stepping down is followed by some regain, with the magnitude unknown.

32 likes 2.1y

customs_ledgerTL3Regular26 Jun 2024#31

21 likes 2.1y

dr_seongTL3Physician8 Jul 2024#42

I read post #40 twice before replying, because I had assumed the opposite.

Titrating on tolerability rather than on the calendar: some people escalate when they tolerate a dose well, others escalate on the prescribed schedule regardless. The published trials used a calendar-based schedule. Tolerability-based escalation has no formal evidence base but is not uncommon in practice.

28 likes 2.1y

s.radichTL2 Moderator23 Jul 2024#57

v.salgado, post #24: I read post #22 twice before replying, because I had assumed the opposite. Steady state means the plasma concentration is stable from dose to dose. That happens around 4 to 5 half-lives. Before that, the concentration is rising with each dose. Escalating before steady state means escalating on incomplete information about the dose you… Go to post

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

27 likes in reply to #24 2y

Read the full topic (61 posts)

This topic was referenced in

Why "dose equivalence" between different incretin analogues is a weak conceptPractice › Dosing & titration · 133 replies
When a dose reduction is the correct response to a side effectPractice › Dosing & titration · 42 replies

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