Teduglutide ↗ is a synthetic version of GLP-2 ↗, a gut hormone that helps the intestine absorb more of what a child eats. For children with short bowel syndrome, whose intestines are too short or too damaged to take in enough nutrition on their own, the drug offers a way to eat their way off parenteral nutrition, the intravenous feeding that keeps them alive but carries infection and liver risk. The FDA approved teduglutide for children in 2019. What has been missing is a long, multicenter look at what three years on the drug actually does.
A new report in Pediatric Research ↗ fills part of that gap, and it carries a caution alongside the good news.
The study drew on the Pediatric Teduglutide Registry (NCT04832087), a 14-center observational study run out of Boston Children's Hospital that enrolled 140 children between May 2021 and December 2022 and followed them for up to three years. Effectiveness was measured in 120 of them.
The feeding numbers moved steadily in the right direction. The share of a child's calories delivered through the IV line fell by an average of 8.3% at six months, 16.5% at one year, 33.0% at two years, and 49.5% at three years. By the third year the average child on teduglutide was getting roughly half as much of their nutrition through the vein as when they started. The proportion who reached enteral autonomy, meaning they came off parenteral nutrition entirely, climbed on a similar curve: 7.5% at six months, 15.2% at one year, 26.4% at two years, and 32.7% at three years. About one child in three was fully weaned by year three.
The caution is in the growth data. The fraction of children who were underweight, defined as a low weight-for-age Z score, rose from 2.3% at baseline to 12.7% at three years, a statistically significant increase (p<0.01). BMI Z scores also declined over the same window. Height held steady, so the children were not falling off their growth curves in stature, but a growing minority were carrying too little weight for their age as they moved off IV nutrition.
That is the tradeoff the registry makes visible. Cutting parenteral calories is the goal, because IV feeding is what drives the catheter infections and liver damage that make short bowel syndrome dangerous. But parenteral nutrition is also a guaranteed calorie floor. As it comes down, the child has to make up the difference by absorbing enough from food, and this registry shows that a meaningful share did not fully manage it. The weaning worked. The weight did not always follow.
There was a second signal worth flagging. Five children developed inflammatory or foveolar polyps in the gut. GLP-2 is a growth factor for intestinal tissue, which is exactly why teduglutide works, and that same proliferative push has raised a long-standing question about what it does to the gut lining over years of exposure. Five cases in 140 children is not a rate anyone can interpret with confidence, but it is a reminder that the drug's mechanism cuts both ways.
None of this argues against teduglutide. A drug that weans a third of children with short bowel syndrome off intravenous feeding within three years is doing something no other therapy does. But the registry reframes the win. This is not a set-and-forget medication. The children who respond are trading a hard IV-nutrition risk for a softer, slower one, and the growth curves say that tradeoff needs watching closely, not assuming.
An earlier single-center report ↗ this year found that about half of children weaned off IV feeding on teduglutide, a higher rate than this multicenter registry. That is the usual pattern. A specialized center with tight follow-up gets better numbers than a 14-site cohort that looks more like everyday practice. The registry's job was never to beat the single-center figure. It was to show what happens when the drug leaves the flagship program, and the answer is that it still works, at a more modest rate, with a growth cost that a single center's careful nutrition team may have caught earlier.