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Topic summary

Splitting a weekly dose in two: the pharmacokinetic argument against — the long version

This is a generated summary. It shows the 9 most-liked posts from a topic of 149, 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.
SL
s.lundgrenTL2 Moderator8 Jul 2024#45
g.haaland, post #16: 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. Go to post

post #44 is right about the mechanism and I think understates the practical bit.

Dose equivalence between different incretin analogues is a weak concept. The molecules differ in structure, half-life, receptor selectivity, and in what has been studied clinically. One mg of semaglutide is not equivalent to one mg of something else in any meaningful sense.

30 likes in reply to #16 2.1y
CD
cannula_driftTL3Regular8 Jul 2024#68

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.

32 likes 2.1y
K
KTurkingtonTL3Regular8 Jul 2024#71
h.eriksen, post #27: 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. Go to post

Worth separating two things that post #67 runs together.

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.

31 likes in reply to #27 2.1y
AR
a.reyesTL4 Admin9 Jul 2024#80
journalclub_wren, post #29: Picking up post #26: that is the part I would want checked first. The four-week escalation interval is a convention from the pivotal trials, not a pharmacological constant. The pharmacological argument is that with a week-long half-life, four weeks approaches steady state and you can assess the dose fairly. That is an argument for not… Go to post

post #79 is right about the mechanism and I think understates the practical bit.

Dose equivalence between different incretin analogues is a weak concept. The molecules differ in structure, half-life, receptor selectivity, and in what has been studied clinically. One mg of semaglutide is not equivalent to one mg of something else in any meaningful sense.

30 likes in reply to #29 2.1y
RV
r.venkatesanTL3Wiki editor9 Jul 2024#88

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.

32 likes 2.1y
B
BBramleyTL3Regular9 Jul 2024#96

This follows post #93 rather than contradicting it.

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.

30 likes 2.1y
RL
r.lundgrenTL2 Moderator10 Jul 2024#112
h.fonseca, post #41: 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.

29 likes in reply to #41 2y
KR
k.redgraveTL2Member10 Jul 2024#119

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 2y
DE
d.eriksenTL2 Moderator10 Jul 2024#123
r.venkatesan, post #88: 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. Go to post

The arithmetic of an intermediate dose: if the label says 1.0 mg and 2.0 mg, a dose strictly between them is off-label by definition. Some people compute it anyway. The reasoning is pharmacological — e.g., "I will split the difference between steps" — but it is reasoning from theory, not from evidence.

31 likes in reply to #88 2y

Read the full topic (149 posts)

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