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ForumsLab Results & BiomarkersHas anyone dealt with kidney function on semaglutide?

Has anyone dealt with kidney function on semaglutide?

Dr.NephBHM_UK Sun, Apr 6, 2025 at 10:14 AM 10 replies 1,603 viewsPage 1 of 2
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Dr.NephBHM_UK
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Apr 6, 2025 at 10:14 AM#1

Writing this once so I can stop repeating it across threads. It is about semaglutide, and it is deliberately narrow — everything I am not confident about is marked as such.

What is actually established

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.

The condition it depends on

"tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.

The practical version

Worth knowing that the injection site changes very little. Abdomen, thigh and upper arm are bioequivalent for semaglutide, so a site change is not a plausible explanation for a bad week.

What I am not sure about

The question I want answered is what the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss. Practical detail welcome, however dull — the duller the better.

— Dr.NephBHM_UK · corrections welcome and will be edited into this post with credit
3 23Dr.CardioMD, EndoResFellow, PharmacoVig_BOS
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Dr.NateNeph
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Apr 6, 2025 at 10:29 AM#2
Dr.NephBHM_UK said:
Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

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.

2 22NauseaFreeNow, SteveThurs
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JessicaH_TX
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Apr 6, 2025 at 10:44 AM#3
Dr.NephBHM_UK said:
Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

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JenPlateau
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Apr 6, 2025 at 10:59 AM#4

Short answer first, then the reasoning. 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".

Last edited: Apr 6, 2025 at 4:59 PM
50 20FitDadDave, RunnerRach, TrialNerd_Beth and 47 others
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FitDadDave
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Apr 6, 2025 at 12:18 PM#5
Dr.NateNeph said:
All true, with one condition: that curve is for people who reached the dose on schedule.

That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.

49 19jason_paloalto, Dr.LeslieOBGYN, MikeNYC_runner and 46 others
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