Nobody knows, and the study usually cited for it cannot say. Diabetic foot complications made up 6.38 of every 1,000 GLP-1 adverse event reports against 11.31 per 1,000 for other diabetes drugs, a ratio of 0.56 [1]. That is a share of a report pile, not a rate in patients. The question underneath is a good one, because people with diabetes lose toes and feet to ulcers that begin as small wounds. The trouble is that the instrument used here answers only whether harm appears more often than expected. It cannot be turned around and asked whether something appears less often than it should, which is the same asymmetry running under the dose-error reports.
What was measured
The FDA’s adverse event database was queried for every report naming a GLP-1 drug between 2005 and 2024, and for every report naming one of the other diabetes drug classes. [1] There were 1,819 of the former and 17,206 of the latter. Diabetic foot complications made up 6.38 per thousand of the GLP-1 pile. The comparison pile carried 11.31 per thousand. That gives a proportional reporting ratio of 0.56, with an interval from 0.54 to 0.59 narrow enough to look like certainty about something.
Semaglutide came out at 0.45, dulaglutide at 0.49 and liraglutide at 0.30, and the pattern held across sensitivity analyses. The consistency is genuine. What it is consistent about is the part that needs care — and the mechanics of the database itself we have covered in a separate piece.
The direction the method runs
A larger evidence map across several safety databases makes the same point from the other end [2]. What that kind of mapping surfaces is the terms reported unusually often — dosing errors, gastrointestinal events, injection-site problems — because those are the only ones the arithmetic can find. Nothing in it is built to notice a complication that failed to turn up at all.
Disproportionality analysis was designed to find signals: to notice when a drug’s reports contain a strange term far more often than the background does, so that somebody can go and investigate properly. Running above the expected share is a reason to look. Running below it is not a finding, because the things that suppress a share are so numerous and so ordinary that no ratio can separate them.
This is the same asymmetry that makes an absent result different from a negative one, arriving through a different door.
The genetic half
The authors also ran a Mendelian randomization, using inherited variation in the GLP-1 receptor gene as a stand-in for the drug, and report that it broadly agreed with the database analysis.
That is a genuinely independent instrument, which is worth more than another pass through the same reports. It also answers a different question. Small lifelong differences in a receptor are not eighteen months of a therapeutic dose in a fifty-year-old. A method that models a lifetime cannot tell you what happens after a year, much as a model trained on one thing keeps getting read as evidence about another.
What would settle it
A cohort with feet in it. Count the people taking each drug, examine them, and record the ulcers — the trial evidence already exists for wound-adjacent outcomes in other conditions, so the design is not exotic.
Until then, the honest summary is the one the authors themselves wrote: preliminary, requiring prospective validation. Weight loss and better glucose control ought to help a diabetic foot, so the hypothesis is reasonable on its face. Reasonable is not the same as demonstrated, and a large database is not the same as a large study.