Glycaemic effects improved rather than worsened in the diabetes work despite the glucagon component, which is the observation that resolves the apparent paradox. It is worth understanding that mechanism before repeating either half of it.
The question in the title: Why a glucagon receptor agonist in a weight-loss compound is not a contradiction — one year on I will give what I have already checked below so nobody repeats it.
Glucagon receptor agonist: what I expected, what I found, and the gap between them.
I am posting the gap rather than a theory about it. My theories about gaps like this one have not held up well.
Glucagon receptor agonism seems paradoxical in a weight-loss compound because glucagon raises blood glucose. The paradox resolves because glucagon agonism also increases energy expenditure and promotes hepatic fat oxidation, and the incretin components offset the glycaemic effect. In diabetes trials, HbA1c improved rather than worsened.
Confirming post #3 from a second method, which matters more than confirming it from a second person.
On identity confirmation more generally: for a compound with no widely available reference material, orthogonal confirmation matters more than usual. A mass result and a chromatographic result together say considerably more than either alone.
Triple agonism at GLP-1, GIP and glucagon receptors is the defining feature and the glucagon limb is the one people find counter-intuitive. It raises energy expenditure and promotes hepatic fat oxidation, and the incretin limbs offset the glycaemic consequence.
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