GIP receptor agonism and the argument about direction

GIP receptor agonism and the argument about direction — setting out what I have, and where I think it stops being reliable.

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

• Column: C8, 4.6 x 150 mm, 3.5 um
• Mobile phase: 0.1% TFA in water / 0.1% TFA in acetonitrile
• Gradient: 14% to 59% organic over 23 minutes
• Detection: 220 nm
• Injection: 16 uL
• Sample: retatrutide, reconstituted to 2.0 mg/mL, injected within an hour

The main peak integrates at 97.8% 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.

Picking up the opening post: that is the part I would want checked first.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

On the opening post — agreed on the reasoning, with one qualification.

Species differences: rodent studies show the same compounds produce effects in rodents that predict human effects reasonably well for semaglutide and tirzepatide. The track record is less clear for novel compounds with less human data.