I would like to know how much of this is established and how much is a reasonable story.
I want to know what the trade-off actually is rather than which option is fashionable.
I would rather have a defensible reason than a marginal improvement.
So which one, and on what grounds?
Answer first: a daily GLP-1 agonist with a C16 fatty-acid acylation, the first of the acylated agents, and the one with the longest continuous clinical record in this class.
The shorter half-life also makes it easier to stop: exposure falls to negligible within about three days rather than five weeks.
The relevant detail is that weight reduction at 3.0 mg in the SCALE programme was around eight per cent at 56 weeks, which is real, modest by 2026 standards, and was impressive when published.
The thirteen-hour half-life is published in the regulatory pharmacokinetic review and is the basis for the daily schedule.
Thirteen-hour half-life, daily dosing, weekly titration. Everything else follows.
edited 19 Mar 2026 by Dr_Ilse_Vandenberg — expanded the table to cover the lower concentration
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Browse resultsThe honest answer is that it is outperformed on weight by everything newer and remains a perfectly reasonable agent with a very long safety record.
LEADER was the cardiovascular outcome trial in type 2 diabetes and reported a reduction in major adverse cardiovascular events, which is what opened the door for the whole class to be regarded as more than glycaemic agents.
For research-grade material, this is a well-characterised molecule with a long history and a correspondingly good supply of published comparator data.
Modest by current standards and with the longest record in the class. Both are true.
The short version: modest weight effect by current standards, solid glycaemic effect, and a cardiovascular outcome trial that established the class effect before anything else did.
Structurally: a C16 palmitic acid attached via a glutamic acid spacer at position 26, plus a lysine-to-arginine substitution at position 34. The acyl chain binds albumin, but less avidly than the diacids used later, giving a half-life of roughly thirteen hours.
The relevant detail is that licensed dosing is 0.6 mg daily as initiation, titrating to 1.8 mg for glycaemia and to 3.0 mg for weight management, with weekly titration steps rather than four-weekly ones because steady state arrives within days.
The C16 acylation strategy is the direct precursor to the C18 and C20 diacid strategies used in the weekly agents, which is a clean illustration of how the class developed.
LEADER is the citation for cardiovascular outcomes, SCALE for weight.
Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.