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.

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

A narrower follow-up, since the general answer is now clear:

What the phase 2 dropout pattern implies about how the phase 3 tolerability will read?

dan_philly said:

For anyone tracking the class: GLP-1 alone gets you appetite, GLP-1 plus GIP adds tolerability and lipid handling, and adding glucagon adds…

Coming at dan_philly’s question from a different direction. The gap between trial results and real-world results is consistent and it is not fraud. Trial participants get titration by protocol, scheduled contact, free drug and dietetic support; removing that infrastructure costs a few percentage points every time it has been measured. When your own curve sits below the published mean, that is the likeliest explanation before anything about you or your material.

Closing the loop on my own question.

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.

NurseLeah_Nash said:

The gap between trial results and real-world results is consistent and it is not fraud.

NurseLeah_Nash has the substance of this right. The condition it depends on is worth stating. 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. A curve that has not flattened is a real finding, but it also means the true plateau is unknown, and phase 2 populations are small and selected.