Glucagon receptor agonism in a weight-loss compound

On the subject in the title: Glucagon receptor agonism in a weight-loss compound Working notes rather than a conclusion.

Posting the method first, because I know what the first three replies will otherwise be.

• Column: C18, 3.0 x 150 mm, 2.6 um
• Mobile phase: 0.1% TFA in water / 0.1% TFA in acetonitrile
• Gradient: 9% to 62% organic over 33 minutes
• Detection: 214 nm
• Injection: 15 uL
• Sample: semaglutide, reconstituted to 0.5 mg/mL, injected within an hour

The main peak integrates at 99% of total area. There is a small feature on the trailing edge that I cannot decide is a shoulder or a baseline artefact, and that is what I am actually asking about.

I read the opening post twice before replying, because I had assumed the opposite.

Bias and desensitisation: receptors can be biased (preferentially activating some downstream pathways over others) and can desensitise over time (responding less to the same stimulus with repeated exposure). Both might affect long-term response to these compounds.

Central versus peripheral action: GLP-1 agonism works through both central nervous system effects (appetite) and peripheral effects (gastric motility, insulin). The balance is not fully characterised.