Does GLP-2 help your gut wall repair and grow?
GLP-2 analogues promote repair and growth of the gut wall and reduce the need for intravenous nutrition in patients with short bowel syndrome. Whether you personally would benefit depends on your situation, so discuss this with your doctor.
GLP-2 stimulates the production of new cells in small pockets of the gut wall (crypts) and at the same time slows the natural die-off of gut cells. This causes the gut wall to grow and repair itself structurally. This mechanism is well described in animal studies and experiments with cells, and makes good biological sense. Whether the same happens in people to the same degree has been less thoroughly studied.
A concrete measure of repair in people is the blood level of citrulline, a substance whose level rises as more functioning gut-wall cells are present. In patients with short bowel syndrome (a condition in which a large part of the small intestine is missing or not working), teduglutide at a daily dose of 0.1 mg/kg produced the largest rise in that value, on average just over 14 µmol/L more than in the comparison group. This points to functional repair of the gut wall.
The strongest evidence in people comes from apraglutide (a GLP-2 medicine given once a week). After 24 weeks, patients needed on average 25.5% less intravenous nutrition, compared with 12.5% in the comparison group. That difference was clear and meaningful: 43% of patients needed the drip for at least one fewer day per week, compared with 27.5% in the comparison group. Stopping intravenous nutrition completely was achieved by a smaller group, and the difference there was not clear enough to draw firm conclusions.
GLP-2 also appears to widen the small blood vessels in the gut and improve its barrier function, but this has so far been too little studied in people to make firm statements about. In mouse studies, GLP-2 protects the gut wall against damage caused by activated immune cells, which is interesting for conditions such as Crohn's disease, but this has not yet been studied in people.
GLP-2 medicines are generally well tolerated: people did not clearly experience more side effects than the comparison group. The most important point to be aware of is that these medicines may also cause existing gut tumours to grow. Up to thirty months of treatment, no increased tumour risk was found in people without known cancer, but animal studies suggest that existing tumours may grow faster. The follow-up period is still too short to rule this out entirely. Always discuss this with your doctor if you use or are considering this medicine.
This answer draws on three overviews of existing studies, a large phase-3 trial in people (apraglutide, 163 patients) and a mechanistic mouse study. The authors of the overviews noted themselves that the available studies were scarce, highly varied, and carried a high risk of bias. This makes the findings in people regarding citrulline and gut repair reliable as a signal, but not as definitive proof. The evidence for gut growth through increased cell production is solid in mice, but less well developed in people. The apraglutide evidence is the strongest human pillar.