This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.
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.
Where I think it is weakest: the comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
So the question, as narrowly as I can put it: why adding glucagon agonism to an anti-obesity drug is not self-defeating, given that glucagon raises blood glucose. Happy to be told the question itself is wrong.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
Dr.AddMedPHL 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.
That holds where the measurement is reliable. Where it is noisy — and a lot of what gets tracked here is noisy — the same reasoning produces confident nonsense.
Dr.AddMedPHL 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.
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 BiochemAnswering the narrow version, because the broad one does not have a single answer. 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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
KevinCompounds said:That holds where the measurement is reliable.
Adding a me-too, because a thread of one person's experience is not much use.