Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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.
Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.
What I am trying to establish is what the phase 2 dropout pattern implies about how the phase 3 tolerability will read. I would rather have one careful answer than five confident ones.
newstart_MO said:The glucagon component looks paradoxical and is not.
Agreed on the substance. I would put less weight on the timescale, because two months of anything is not enough to distinguish a trend from a wobble.
newstart_MO said:The glucagon component looks paradoxical and is not.
I would rather people stopped quoting the 24% as if it were a licensed outcome. It is a phase 2 result in a few hundred participants with no cardiovascular endpoint and no long-term safety data, and this board has a habit of treating pipeline numbers as settled.
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Browse GL BiochemThis one has a reasonably settled answer, so here it is. 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.
julia.endo said:I would put less weight on the timescale, because two months of anything is not enough to distinguish a trend from a wobble.
This matches mine closely enough to be worth saying so out loud. Posting only so the count is not one.