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Two more people in a thousand

Pooling 55 trials and 106,395 participants, gallstones and reflux went up and almost nothing else did. The frightening items on the list came back null.

Neil Sanders5 min read
Extra cases per 1,000 people treatedgallstones2 more in 1,000reflux4 more in 1,00055 trials, 106,395 participants

A risk ratio of 2.19 sounds like a reason not to buy something. It is four people in a thousand. Both statements describe the same result.

What was pooled

Five databases were searched for placebo-controlled randomized trials in type 2 diabetes, overweight or obesity, and fatty liver disease. Fifty-five trials qualified, covering 106,395 participants. [1] The review looked for a specific list of serious gastrointestinal and biliary events rather than for nausea, which is a different and much commoner problem — and one sellers already charge differently for.

Two things went up

Gallstones. The risk ratio was 1.46, 95% CI 1.09 to 1.97, which the authors translate as about 2 extra cases per 1,000 people treated. Reflux. The risk ratio was 2.19, 95% CI 1.48 to 3.25, or about 4 extra cases per 1,000.

Read either way round, the facts do not change. A 46% increase and 2 people in 1,000 are the same finding. Which number you meet first usually decides how you feel about it.

What did not go up

Everything else on the list. Pancreatitis. Bowel obstruction. Paralytic ileus. Perforation. Gastrointestinal bleeding. Ischemia. Ulceration. Gastritis. Esophagitis. Cholecystitis, cholangitis and cholestasis. Gastroparesis. Across 55 trials the review found little or no effect on any of them.

That is the more useful half and it is the half nobody repeats. Several of those are the exact things people have read alarming stories about. A pooled null across a hundred thousand randomized participants is about as good as evidence of absence gets.

Why this page is on a price site

Because a gallstone is a bill. Reflux usually means a cheap daily tablet. Symptomatic gallstones can mean imaging, a specialist, and sometimes surgery to remove the gallbladder. None of that is in the monthly figure, and the monthly figure is already not the bill.

Two in a thousand is a small number and it is not zero. Priced across a year of buyers, somebody pays it. The sensible response is not to avoid the drug. It is to know that the published price is a floor and to keep the rest of the arithmetic in view.

What to ask before ordering

One question does most of the work. If something goes wrong, who do I call, and how fast? A gallstone attack is an emergency room visit, not a support ticket. Most sellers here publish very little about clinical access, and none of it appears beside the price.

Frequently asked

How much does gallstone risk actually rise?
The pooled risk ratio was 1.46, 95% CI 1.09 to 1.97, which the review states as roughly 2 extra cases per 1,000 people treated. Both framings describe the same result.
Does it cause pancreatitis?
Across 55 placebo-controlled trials and 106,395 participants, the review found little or no effect on pancreatitis, along with bowel obstruction, ileus, perforation, bleeding and gastroparesis.
Is the risk higher at higher doses?
It looked that way and the difference did not reach statistical significance. The same applies to trials in obesity and to the agents producing the most weight loss, so treat it as a hypothesis rather than a dosing rule.
What should I budget for?
Reflux is usually a cheap daily tablet. Symptomatic gallstones can mean imaging, a specialist and sometimes surgery, none of which sits inside a monthly subscription price.

Sources

  1. [1] Chiang H, et al. (2025). Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis Gastroenterology. PMID 40499738

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