Semaglutide versus liraglutide head to head: reading STEP 8 carefully — setting out what I have, and where I think it stops being reliable.
I would like to disagree carefully with the settled view on Semaglutide versus liraglutide, and I would like to be argued out of it if the disagreement is bad.
The disagreement is about one step, not about the conclusion. If the step holds I withdraw it entirely.
Confirming the opening post from a second method, which matters more than confirming it from a second person.
On identity confirmation: a mass close to 4113.6 Da on the intact molecule is consistent with semaglutide and is also consistent with several closely related species. Mass narrows the field; it does not close it, and no certificate should be read as though it did.
On the opening post — agreed on the reasoning, with one qualification.
Semaglutide's structure is a modified backbone with a C18 diacid attached through a spacer. The acylation is the reason for the long half-life and it is also the reason a plain sequence comparison against native GLP-1 is misleading about how the molecule behaves.
Right, and stated more narrowly than I would have dared to state it.
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.
That has held every time I have looked, which is not the same as always.
On the injection-day question: the labelling for licensed semaglutide allows the day to be changed provided at least two days separate the two injections. That interval is not arbitrary — it is what stops two doses stacking inside one absorption window.
The honest answer is that it depends, and here is what it depends on.
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Tracking semaglutide's approved indications across jurisdictions, dated — does this still hold?
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+58 | 62 | 49k | 20mo |
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Coming back to: What the published dose-response for semaglutide actually looks like above 2.4 mg
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+23 | 27 | 9.9k | 1mo |
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+16 | 20 | 17k | 13mo |
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Coming back to: Semaglutide in people without diabetes: what the evidence base looks like
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+41 | 46 | 1.2k | 4mo |
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+15 | 19 | 4.4k | 13mo |
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Heart failure with preserved ejection fraction: symptom endpoints
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+19 | 23 | 311 | 12d |
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Journal club: SURPASS-2 and the semaglutide 1 mg comparator
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+71 | 76 | 52k | 21mo |
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2 | 31k | 13mo | |
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Revisiting: Gallbladder disease risk with rapid weight loss
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2 | 2k | 9mo | |
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Follow-up: Tirzepatide's shorter half-life and its one practical consequence
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+130 | 137 | 11k | 19mo |