Answering the narrow version, because the broad one does not have a single answer. The glucagon component looks paradoxical and is not. Glucagon receptor agonism raises energy expenditure and drives hepatic fatty-acid oxidation, and its hyperglycaemic tendency is offset by the GLP-1 arm's insulin secretagogue effect. Net result: intake down from GLP-1/GIP, expenditure up from glucagon, glycaemia neutral or improved. It is a balancing act, and it is why the liver-fat results are the most interesting part of the dataset.

That is the short version; the long version is somebody else's post.

DanielChem_CHI ↑ said:

The glucagon component looks paradoxical and is not.

Fair, but phase 2 tolerability figures rarely survive contact with phase 3 scale. Triple agonism means three receptor systems generating adverse events, and the dropout column is the one I would read first when the larger trials report.

SleepDoc_PDX ↑ said:

Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

This is my experience too, for whatever a second data point is worth. The detail I would add is minor and it is already implied above.

Clinical perspective, offered as context rather than as advice.

I want to bring up the cardiovascular angle on cardiovascular risk.

The SELECT trial demonstrated a 20% reduction in MACE with semaglutide 2.4mg[1]. This is practice-changing because the CV benefit appears to be independent of the degree of weight loss — suggesting direct vascular and anti-inflammatory mechanisms.

For cardiovascular risk, this means we need to think beyond the primary outcome and consider the cardiovascular implications. The all-cause mortality reduction (HR 0.81) is the most clinically meaningful signal.