Semaglutide versus liraglutide in STEP 8: semaglutide produced greater weight reduction and the discontinuation rates differed. But the trial was open-label for the dosing schedule, which admits expectation effects. Weekly versus daily itself is part of the comparison, not a confounding variable to be removed.
What SELECT changed about how semaglutide is discussed, and what it did not posts 121–133
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.
The STEP programme populations were selected: enrollment criteria required baseline body mass index over 30, no recent blood pressure crisis, no recent retinopathy, no renal disease at the time. Applying results from that population to someone well outside it is an extrapolation and should be called one.
Coming back to post #121, because the follow-up matters more than the original answer.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
Picking up post #121: that is the part I would want checked first.
Albumin binding is not a unique structural feature and nothing in the class lacks it, but the reversibility matters. Semaglutide binds albumin covalently through a fatty side chain, which creates a very long half-life at the cost of sequestering the free form. That is a trade-off and it is the trade-off that allows weekly dosing.
The mass figure differs between sources because of how the different entities report it. The monoisotopic mass of the bare peptide is one number; the mass including the acylation is another. Different sources emphasise different details.
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.
I read post #125 twice before replying, because I had assumed the opposite.
Semaglutide versus liraglutide in STEP 8: semaglutide produced greater weight reduction and the discontinuation rates differed. But the trial was open-label for the dosing schedule, which admits expectation effects. Weekly versus daily itself is part of the comparison, not a confounding variable to be removed.
On post #125 — agreed on the reasoning, with one qualification.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
post #129 answers the question as asked. The question underneath it is different.
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.
Picking up post #128: that is the part I would want checked first.
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.
Coming back to post #130, because the follow-up matters more than the original answer.
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.
Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.
This topic was referenced in
- Molecular mass of semaglutide and why the figure differs between sourcesCompounds › Semaglutide · 110 replies
Suggested topics
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
Revisiting: Semaglutide formulation: what is in the licensed product besides the peptide
Posting this under the heading it deserves: Revisiting: Semaglutide formulation: what is in the licensed product besides the peptide Everything below is what sits behind that. I have seen SURMOUNT-4 ( JAMA ,…
|
+72 | 77 | 7.2k | 19mo |
|
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…
|
+1 | 5 | 11k | 20mo |
|
Semaglutide and alcohol: what is actually documented
Posting this under the heading it deserves: Semaglutide and alcohol: what is actually documented Everything below is what sits behind that. I have seen STEP 8 ( JAMA , 2022) cited in support of a claim I do…
|
+14 | 18 | 10k | 2d |
|
Semaglutide in people without diabetes: what the evidence base looks like
Semaglutide in people without diabetes: what the evidence base looks like Writing it up because I had to work it out twice and would rather nobody else did. Session topic: SUSTAIN 6 ( N Engl J Med , 2016).…
|
+2 | 6 | 18k | 17mo |
|
Molecular mass of semaglutide and why the figure differs between sources
Molecular mass of semaglutide and why the figure differs between sources — setting out what I have, and where I think it stops being reliable. Comparing SURMOUNT-2 ( Lancet , 2023) with STEP 4 ( JAMA , 2021)…
|
+101 | 110 | 12k | 16h |
Related topics — sharing the tags STEP programme, type 2 diabetes, randomised trial
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
What TRIUMPH is designed to answer, and why we should not pre-empt it
What TRIUMPH is designed to answer, and why we should not pre-empt it I have a specific reason for asking rather than idle curiosity, and the context is below. I have seen SURPASS-4 ( Lancet , 2021) cited in…
|
+4 | 8 | 142 | 6h |
|
About the Journal club category
Our recurring session. One named paper per topic, methods first, conclusions last. Everyone reads before posting. This post is a community wiki: any member at trust level 3 or above can edit it, and every…
|
+2 | 6 | 12k | 16mo |
|
Gastro-oesophageal reflux: improving or worsening?
The question in the title: Gastro-oesophageal reflux: improving or worsening? I will give what I have already checked below so nobody repeats it. Asking about a population rather than about a person. The…
|
+54 | 58 | 8.2k | 1mo |
|
Second pass at: Obstructive sleep apnoea and a hard endpoint in this class
Second pass at: Obstructive sleep apnoea and a hard endpoint in this class — setting out what I have, and where I think it stops being reliable. Asking about a population rather than about a person. The…
|
2 | 726 | 14mo | |
|
Historical amylin analogues and what happened to them
Posting this under the heading it deserves: Historical amylin analogues and what happened to them Everything below is what sits behind that. I have seen SURPASS-2 ( N Engl J Med , 2021) cited in support of a…
|
+29 | 36 | 31k | 1d |