Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.
The gallbladder signal is real and it is mostly the weight loss, not the drug. Rapid loss increases biliary cholesterol saturation and reduces gallbladder motility, which is the classic recipe for stones — the same effect appears after bariatric surgery and in very-low-calorie dieting, without any GLP-1 involved. Trial data shows a modest absolute increase in cholelithiasis, concentrated in faster losers.
Where I think it is weakest: the subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.
What I actually want to know is how much of the gallbladder signal is the drug and how much is simply the rate of weight loss, because the answer changes what you can do about it. Not looking for reassurance. Looking for the part I have got wrong.
PharmacoVig_BOS said:The gallbladder signal is real and it is mostly the weight loss, not the drug.
Agreed, and subgroup analyses deserve particular suspicion. With enough subgroups something is significant by chance, and pre-registered subgroups are a different animal from ones found afterwards.
PharmacoVig_BOS said:The gallbladder signal is real and it is mostly the weight loss, not the drug.
Pushing back on PharmacoVig_BOS here. I would add the less popular caveat: these trial populations under-represented several groups, older adults and the highest BMI categories among them. The results probably generalise, and "probably" should be stated as an assumption rather than dropped.
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View ResultsTaking the question as asked, rather than the general version of it. 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.
Dr.NateNeph said:Agreed, and subgroup analyses deserve particular suspicion.
This matches mine closely enough to be worth saying so out loud. I had assumed I was the exception until I read this.