SOUL trial: semaglutide cardiovascular outcomes in T2DM — design overview

NurseLeah_Nash said:

Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

This answered a question I did not know how to ask.

Adding the clinical framing, because it changes how the question reads.

Dr.CardioMD 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.

LipidDoc_ATL said:

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

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.

Ask again with the specifics and you will get a better answer than this one.

One concrete data point for the thread. Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.

Worth separating that from cardiovascular outcomes, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

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