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ForumsSemaglutide (Ozempic / Wegovy)Has anyone dealt with month 2 and i have lost nothing - normal???

Has anyone dealt with month 2 and i have lost nothing - normal???

MarkLI_maint Sat, Jun 14, 2025 at 11:18 AM 12 replies 1,458 viewsPage 1 of 3
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MarkLI_maint
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Jun 14, 2025 at 11:18 AM#1

Six months in at 2.4mg. The first four months were close to the trial curve and the last two have been flat, which is roughly what the STEP 1 figure predicts if you read the tail rather than the headline.

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.

What I am after is whether anyone has held at a sub-maximal dose long term and kept the result, or whether the maintenance data only exists at 2.4mg.

Practical detail welcome, however dull — the duller the better.

7 2RunnerRach, TrialNerd_Beth, HPLC_Greg and 4 others
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TrialNerd_Beth
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Jun 14, 2025 at 1:10 PM#2

Answering the narrow version, because the broad one does not have a single answer. 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.

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jason_sac26
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Jun 14, 2025 at 3:02 PM#3
TrialNerd_Beth said:
The mechanism that matters here is not stomach emptying, it is central.

Agreeing with TrialNerd_Beth, and the qualification matters more than the agreement. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.

Last edited: Jun 14, 2025 at 5:02 PM
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jennifer_SEA
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Jun 14, 2025 at 4:54 PM#4
MarkLI_maint said:
The first four months were close to the trial curve and the last two have been flat, which is roughly what the STEP 1 figure predicts if you read the…

All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.

Happy to go further on any of that.

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EndoResFellow
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Jun 15, 2025 at 3:56 AM#5

Clinical perspective, offered as context rather than as advice.

MarkLI_maint said:
...but the FDA says semaglutide...

Interesting point. I want to add some regulatory nuance: the FDA labeling reflects the specific clinical trial data submitted for approval. Real-world clinical practice often extends beyond the FDA label based on emerging evidence and clinical judgment.

Example: semaglutide was first approved for diabetes (Ozempic), then obesity (Wegovy). The molecule didn't change — our understanding of its applications expanded. Similarly, semaglutide may evolve as more data accumulates.

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