PedsEndoPhilly said:

The dose-response is real but shallow at the top.

Saving this. It is the first explanation that did not require me to already understand it. Sending this to two other people who asked me the same thing last week.

From the other side of the consultation, briefly.

MASHdoc_SA 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.

Dr.LipidDallas said:

Steady state is the thing most people miss.

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.

Adding the numbers, since they settle part of this. With resmetirom now available for MASH, combination approaches are being explored, so the standard of care in this area is moving faster than most threads assume.

Happy to go further on any of that.

Moderator note: leaving this open. It is being argued well and the disagreement is the useful part. Carry on.