you cannot tell which of the two is doing what in a combination and i stopped pretending i could
#cagrilintide 2025-11-03
Monday43 messages11 participantstimes are UTC
Highlights from this day
- noct.titrate — thats the cleanest one sentence version ive read 16:49
- noct.titrate — rough shape of it, and im rounding because the exact figures depend which estimand you read 17:33
- ari_arrives — so the marketing version is oversold and the mechanism version is fine 17:41
- VialBot — archive lookup: `CagriSema` in 118 lines, first on 2024-02-11. related channels #semaglutide #maintenance #side-effects. 19:04
separate days
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changed my mind on this, i started thinking amylin was the interesting bit and now i think its the pairing
whats REDEFINE testing exactly
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is there a reason people titrate this over more weeks than the others
💀1🎉7
how slow are people titrating this compared to tirzepatide
titrating dead slow
held at 0.5 for 5 months on monotherapy before i touched it again
the fullness effect hasnt faded over 11 months, unlike my semaglutide appetite curve
anyone got two PeptideMeter results on the same HJ lot for this
did anyone add this to an existing tirzepatide dose rather than starting both
i keep the two on separate days so if something goes wrong i have a chance of knowing which, anyway
€120 for a 40 vial and it lasts me longer than the GLP-1 does at my doses
someone explain why cagri plus sema is supposed to be more than the sum
the argument is that amylin and GLP-1 satiety signalling converge but do not overlap completely
so you recruit two partly independent pathways instead of pushing one of them harder
and the practical version is you get more effect without having to escalate either component into its own side effect ceiling
thats the cleanest one sentence version ive read
✅11
and does the trial data support it
the combination beat both single agents. mean weight reduction landed just over 20%
and importantly it had cagrilintide alone and semaglutide alone as separate arms, so you can actually see the components
which almost no combination trial bothers to do, credit where its due
rough shape of it, and im rounding because the exact figures depend which estimand you read
| Arm | 68 wk weight change | Comment |
|---|---|---|
| CagriSema | just over -20% | the headline |
| semaglutide 2.4 alone | mid teens | consistent with STEP |
| cagrilintide 2.4 alone | around -12% | monotherapy is not nothing |
| placebo | small |
so the combo is roughly sema plus a bit, not sema plus cagri
thats the fair reading and it is the main criticism of the additive story
partly additive. not fully. which is what you would expect from partly overlapping pathways
so the marketing version is oversold and the mechanism version is fine
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yes. thats a good summary of most combination pharmacology honestly
the number that surprised people was the tolerability. adding a second agent did not double the misery
it also did not hit some of the more optimistic pre trial expectations, which is why the reaction was oddly muted
expectations were doing a lot of work there
expectations always are
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is REDEFINE one trial or a programme
a programme. different populations, including a diabetes one, and the pattern is what you would guess — smaller weight loss in type 2
why smaller in diabetes again
same reasons as everywhere else, and nobody has a clean answer. its in #semaglutide about six times
archive lookup: CagriSema in 118 lines, first on 2024-02-11. related channels #semaglutide #maintenance #side-effects.
2024, feels longer
everything about this field feels longer than it is
the not escalating into your own ceiling point — is that the actual reason to prefer a combo over just more sema
its the strongest reason, yes. two moderate doses instead of one maximal dose. whether that plays out over years, nobody knows yet
we will find out slowly and in public, like always