Adding the clinical framing, because it changes how the question reads.

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.

From the other side of the consultation, briefly.

Senior perspective on cardiovascular risk: I'm 69 years old and started this journey skeptically. My endocrinologist recommended it after years of failed interventions.

11 months later: down 57 lbs, more mobile, pain reduced, medications simplified. My quality of life has improved dramatically. I wish this existed 20 years ago.

To other older adults hesitating: the SELECT trial proved benefit in our age group. You deserve to feel good in your body regardless of age.

sean_dublin said:

Senior perspective on cardiovascular risk: I'm 69 years old and started this journey skeptically.

Same experience, arrived at from the opposite direction. I had assumed I was the exception until I read this.

sean_dublin said:

Senior perspective on cardiovascular risk: I'm 69 years old and started this journey skeptically.

Adding the part of the answer the thread has not reached. 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.

Worth separating that from retatrutide, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. Thread quality here is what the rules are for. Keep it up.