GLP-2 Shows Promise as a Treatment for Gastrointestinal GVHD

A small study of glucagon-like peptide 2 (GLP-2) drug as a treatment for steroid-refractory acute graft-versus-host disease (GVHD) yielded promising results, with 11 of the 17 patients having a complete or partial response, according to a study published in the journal Bone Marrow Transplantation.

Acute GVHD is a complication of allogeneic stem cell transplants, the type of stem cell transplant when cells come from a donor, often a close relation, rather than from the patient (which is called an autologous stem cell transplant). In simplified terms, GVHD develops when T cells in the donated stem cells or attack the patient’s cells because they “see” the patient’s cell as foreign. The skin, gastrointestinal tract, and liver are the parts of the body that are most commonly affected.

Gattex (teduglutide), the GLP-2 assessed in this study, was approved by the FDA in 2021 as a treatment for short-bowel syndrome. Apraglutide is another GLP-2 drug. It is also being developed primarily as a treatment for short-bowel syndrome, but researchers are also assessing it as a treatment for GVHD with gastrointestinal features.

Corresponding author Robert Zeiser, M.D., a professor at the University of Freiburg in Germany, and his colleagues noted that preclinical data suggests that acute GVHD causes a loss of intestinal neuroendocrine L cells, leading to lower levels of GLP-2. Zeiser and his colleagues reported the results of a study in mice in the journal Blood in 2020 that showed that Gattex promoted the regeneration of Paneth cells and intestinal stem cells in the intestine and that, in turn, improved the production of antimicrobial peptides.

Promising results

For this study, they retrospectively analyzed what occurred in 17 patients with acute GVHD. All of them had been treated with corticosteroids, and 15 had been treated with Jakafi (ruxolitinib). Ten of the patients had been treated with a TNF inhibitor (either Remicade [infliximab] or Enbrel [etanercept]) before Gattex, and nine with alpha1-antitrypsin. Gattex, which is delivered with subcutaneous injection, was given in the same doses used when it is a treatment for short-bowel syndrome. The treatments lasted between five and 81 days, with 22.8 days being the average. Zeiser and his colleagues reported that most patients responded during the first 40 days.

Seven (approximately 40%) of the 17 patients experienced complete remission after treatment with Gattex, and four (approximately 25%) had a partial response, which was defined as histological or clinical improvement. Zeiser noted, though, that this meant that more than a third of patients had not responded to Gattex. The relatively short amount of time that the patients were treated is one possible explanation, they wrote. Five of the six nonresponders had been treated for just two weeks or less.

They report that the Gattex was well tolerated with no treatment-associated cytopenia and just one patient discontinuing treatment because of headaches and constipation. One patient needed to be treated for reactivation of cytomegalovirus, but the reactivation occurred before treatment with Gattex.

Robert Zeiser, M.D.

In an email interview, Zeiser said that although his group has conducted preclinical and clinical studies of only GLP-2s, in theory, the GLP-1s might also work for intestinal GVHD. The GLP-1s include semaglutide, sold as Ozempic for diabetes and Wegovy for weight loss, and tirzepatide, which is sold as Mounjaro for diabetes and Zepbound for weight loss.

Zeiser said he and his colleagues are planning to publish a more detailed biomarker analysis in these patients, and he mentioned hopes for a prospective trial with teduglutide (he used the generic, not the brand name). He noted that apraglutide and teduglutide are similar, although apraglutide has a longer half-life and higher activity. “The GLP-2 drugs are very promising because they do not induce immunosuppression,” he said.

But apraglutide’s path to approval and launch swerved in April 2025 when its maker, Boston-based Ironwood Pharmaceuticals, announced that FDA officials saw a need for a confirmatory phase 3 trial after results from the drug’s STARS phase 3 trial showed that the exposure and dose delivered “were lower than planned due to dose preparation and administration,” according to an Ironwood news release.

The news release said the company had engaged Goldman Sachs & Co. LLC to “explore strategic alternatives for the company to maximize value for stockholders.”