Retatrutide and blood pressure — looking for input

Taking the question as asked, rather than the general version of it. 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.

julia.endo 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.

AmyNC_wife said:

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

Mine went the same way, slower. Posting only so the count is not one.

From the other side of the consultation, briefly.

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.