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ForumsDosing & ProtocolsSemaglutide titration: 0.25→0.5→1.0→1.7→2.4mg optimal schedule Page 4

Semaglutide titration: 0.25→0.5→1.0→1.7→2.4mg optimal schedule

Dr.Martinez Mon, Feb 26, 2024 at 4:00 PM 332 replies 13,278 viewsPage 4 of 20
PurityPaulOR
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Feb 28, 2024 at 11:15 AM#16
VanRx_Mike said:
Dr.Martinez said: ...but the FDA says semaglutide...

Same position here, arrived at the long way round. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

15 15Dr.LeslieOBGYN, MikeNYC_runner and 12 others
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SallyK_inj
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Feb 28, 2024 at 3:13 PM#17
PurityPaulOR said:
The dose-response is real but shallow at the top.

Agreed on the arithmetic, with one condition: holding indefinitely at a dose that is not doing anything is not patience, it is a stall with a nice name. The distinction is whether appetite has changed at all at the current step.

14 14bbq_ray_KC, oliver_london, tane_welly and 11 others
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HealthEcon_DC
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Feb 28, 2024 at 7:11 PM#18
PurityPaulOR said:
The dose-response is real but shallow at the top.

Adding the part of the answer the thread has not reached. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.

Last edited: Feb 28, 2024 at 9:11 PM
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VendorMark
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Feb 28, 2024 at 11:09 PM#19

One concrete data point for the thread. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.

12 12Dr.PeteFamMed, claudia_zurich, nancy_portland and 9 others
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Admin
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Feb 29, 2024 at 3:07 AM#20

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful.

Last edited: Feb 29, 2024 at 7:07 AM
40 15PeptideSynthNJ, Dr.KarenChen, Dr.NateNeph and 37 others
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