Can an existing diabetes medicine prevent graft-versus-host disease after stem cell transplant?

January 2021 Science Willem van Altena
Stem Cell Research Pipette

One of the greatest risks involved with stem cell transplantation for the treatment is acute graft-versus-host disease (GVHD), in which the newly imported cells attack the patient’s own cells. Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center recently published promising findings in the New England Journal of Medicine on new ways to prevent GVHD using an existing diabetes medicine.

GVHD occurs in more than 30% of stem cell transplant recipients, an can lead to severe adverse effects and even death. An existing drug, sitagliptin, that is used for the treatment type-2 diabetes, was found to be effective in reducing the risk of GVHD. Lead researcher professor Sherif Farag, MD, PhD is medical director of the hematological malignancies and bone marrow and blood stem cell transplantation at IU Health. In a clinical study involving 36 patients, the effect of sitagliptin was remarkable.

New approach

All 36 stem cell transplant patients were treated orally with sitagliptin, and within 100 days after the transplant only 2 of them developed acute GVHD, which is about 5%. Normally, GVHD occurs in 34% to 51% of recipients in the first three months after the procedure. According to Farag, the numbers are encouraging. “This result is significant and offers a new approach and a new target for inhibition of graft-versus-host disease. We achieved a much lower rate than we could have hoped.” Furthermore, sitagliptin is relatively cheap and easy to administer orally.

Sitagliptin targets an enzyme called dipeptidyl peptidase-4 (DPP-4), which is involved in a variety of processes in the body. It is used for Type 2 diabetes to improve insulin secretion and glucose control. Co-author Hal Broxmeyer, PhD previously found that DPP-4 regulates blood cell production and explored if taking sitagliptin would improve engraftment for cord blood transplants. While there seemed to be some improvement in engraftment of cord blood transplants, one striking finding was the patients had a much lower rate of acute graft-versus-host disease than expected. Farag’s lab took on that data and found targeting DPP-4 with sitagliptin inhibits the immune T cell activation that leads to GVHD.


The 36 patients involved in the trial were between 18 and 60 years old and suffered from either acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS). The patients in the study received sitagliptin orally one day before their transplant and the day of their transplant, plus 14 days after their transplant. Significantly, sitagliptin did not cause hypoglycaemia or low blood sugar levels in patients, despite being administered in a much higher dose than is common for the treatment of diabetes.


The researchers caution that these findings are based on a relatively small group of patients, and a larger multi-center randomized study is needed to confirm them. The researchers hope to be able to explore combination therapies with sitagliptin.


Sherif S. Farag, M.D., Ph.D., Mohammad Abu Zaid, M.D., Jennifer E. Schwartz, M.D. et al. Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease. Published January 7, 2021, N Engl J Med 2021; 384:11-19 doi: 10.1056/NEJMoa2027372.