Retatrutide and blood pressure — 6 month update

DataDave said:

The phase 2 numbers were about 24% mean weight loss at 48 weeks on the top dose, with the curve still descending at the end of the study.

This is where I part company with the consensus forming above. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

I would rather be corrected than agreed with, if it comes to it.

One concrete data point for the thread. For anyone tracking the class: GLP-1 alone gets you appetite, GLP-1 plus GIP adds tolerability and lipid handling, and adding glucagon adds expenditure and liver-fat reduction. Each addition also adds a receptor system that can generate side effects.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

Dr.SurgeonPGH said:

The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

Dr.SurgeonPGH said:

...we don't know the long-term effects of cardiovascular risk...

This is a fair point, and I think intellectual honesty requires acknowledging it. GLP-1 agonists in their current form have ~8-10 years of human exposure data. That's not nothing, but it's not 30+ years either.

However: the risk-benefit calculation should also consider the KNOWN long-term effects of untreated obesity — diabetes, cardiovascular disease, cancer, joint destruction, reduced lifespan by 5-10 years.

Uncertainty about GLP-1 long-term safety vs certainty about obesity consequences. The calculus seems clear to me, but reasonable people can disagree.

One thing that is still open after RegAffairsDC’s answer:

Why adding glucagon agonism to an anti-obesity drug is not self-defeating, given that glucagon raises blood glucose?

Reporting back.

Rereading it with the dropout table open changed my view. I still think it is the most interesting molecule in the pipeline; I no longer think the 24% is the number that will end up on a label.