This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.
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 follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
What would genuinely help is knowing why adding glucagon agonism to an anti-obesity drug is not self-defeating, given that glucagon raises blood glucose. I would rather have one careful answer than five confident ones.
Dr.ObesityLA said:The glucagon component looks paradoxical and is not.
Agreed, with the usual condition: that holds for the average and this board is a collection of individuals. A population claim and a personal prediction are different things and get quoted interchangeably.
Dr.ObesityLA 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 BiochemShort answer first, then the reasoning. 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.
Dr.KarenChen said:Agreed, with the usual condition: that holds for the average and this board is a collection of individuals.
Mine went the same way, slower. Posting only so the count is not one.