Follow-up: Semaglutide versus liraglutide head to head: reading STEP 8 carefully

Semaglutide versus liraglutide head to head: reading STEP 8 carefully — setting out what I have, and where I think it stops being reliable.

I have seen FLOW (N Engl J Med, 2024) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

Picking up the opening post: that is the part I would want checked first.

Is there a ceiling dose beyond which the effect plateaus? The trials did not study that because they stopped at 2.4 mg. Some people report trying higher doses, but trial data is absent and off-label dosing enters territory this site does not advise on.

On the opening post — agreed on the reasoning, with one qualification.

The C-cell question: semaglutide triggered medullary thyroid carcinoma in rodent toxicology studies. A signal in rodents does not automatically appear in humans, but it is the reason the compound is contraindicated in people with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.

Approved indications differ by jurisdiction and change. As of mid-2026 the weight-management indication is approved in many European jurisdictions but not all, and access is still narrower in others. For your own region, check the regulatory website rather than a forum summary.

On alcohol: the labelling does not contraindicate it, but it raises gastric irritation risk and semaglutide already does that. There is no published interaction study and the conservative position is to limit it if you are titrating or if gastrointestinal symptoms are troublesome.

The opalescent appearance in semaglutide solutions is occasionally noted and the mechanism is unclear. It does not appear to correlate with product failure in practice. Visible particles or frank cloudiness is different and would be reason to contact the supplier.